Organ Systems 1 Exam 1 Flashcards
Eukaryotic Cells
Eukaryotic Cells
Cell Membrane
- What are the three types of cytoskeleton and what are their functions?
- What are the three types of cytoskeleton and what are their functions?
Microtubules
Microtubules formed in centrioles
• Centrosome = microtubule organizing
complex MTOC, organelle near nucleus
with 2 centrioles and protein matrix
• Microtubules formed by polymerization of
tubulin proteins extend out from the
centrioles
Organelles
- How does a lysosome deal with a bacterium?
- How does a lysosome deal with a bacterium?Lysosomes
• Contain hydrolytic enzymes
necessary for intracellular
digestion of metabolites and
foreign substances; pH
sensitive
• All cells have them (except
rbc), but are mostly found in
wbc, esp. phagocytes (a type
of wbc)
• Phagocytosis, a specific form
of endocytosis, incorporate
particulate matter by
vesicular internalization of
solids such as bacteria and
proteins
• Vesicles with foreign matter
are fused with lysosomes
where the enzymes digest the
particulate matter to be
exocytosed; this repairs
damage to cell membrane
• Endogenous proteins and
organelles are vesiculated and
fuse with lysosomes
General Functions of the Cell & Cellular Events of Metabolism
GENERAL FUNCTIONS OF THE CELL
1. Proliferation: mitosis or meiosis
2. Differentiation into cell types
3. Metabolism converts nutrient energy into new cell products, eg. proteins & nucleotides which remain in
the cell or are secreted
• Intracellular products are for: cell structures, metabolic enzymes , cell signaling pathways from
membrane into cytoplasm
• Secreted products used for: extracellular matrix , cell-to-cell communication
Functions require external stimuli:
• signaling factors to change activity, divide, or differentiate
• food and oxygen for metabolism
- What are nucleotides? What are the nucleobases and how do they pair up in DNA?
DNA (deoxyribose nucleic acid)
- Double stranded chain of nucleotides linked by hydrogen bonds
- Each nucleotide consists of a 5-carbon sugar (deoxyribose), a nitrogen containing nucleobase attached to the sugar, and a phosphate group.
- DNA/RNA nucleobases are – Pyrimidines: cytosine, thymine, uracil
(in RNA) – Purines: guanine and adenine
- Pyrimidines and purines pair up via hydrogen bonds to form the double helix
- Nucleobase pairs – Adenosine – Thymidine – Guanosine – Cytidine
DNA has various functions, notably:
• •
Cell proliferation /cell division
– Perpetuate organismal traits into next generation of cells (and organisms)
Protein synthesis
– Proteins acting as enzymes are essentialcatalystsfor cellular activities
DNA & Chromosomes
DNA is packaged within histone proteins and
condensed into chromosomes
- The complex of histone proteins and DNA is called chromatin.
- Chromatin is organized into nucleosomes which consist of DNA (orange) wrapped around histone octamers (purple).
- Regions of nucleosomes can either be condensed into heterochromatin or be opened into an extended form, euchromatin. (more on all this later)
DNA Encodes…
DNA encodes the linking of amino acids into proteins
Proteins are chains of amino acids (polypeptides), linked by peptide bonds
Amino acids consist of a central carbon-hydrogen surrounded by: • amino group (NH3) • carboxyl groups (COOH) • R - Unique polar or non-polar side chains of various constituents
– Side chains determine properties of the protein
Amino acids are polar or non-polar depending on R group • Polar R groups are hydrophilic • Non-polar R groups are hydrophobic
- What is meant by hydrophobic and hydrophilic amino acids? What effect do they have on protein configuration?
- What is meant by hydrophobic and hydrophilic amino acids? What effect do they have on protein configuration?
Amino acid (AA) chains self-organize into complex structures (primary to
quaternary).
– 3-D structure of protein is determined by the order of the amino acids
• Protein folding is produced by non-covalent bonds among amino acids :
– hydrogen bonds, ionic bonds, Van der Waal’s attraction, hydrophobic
force
• Hydrophobic forces among AA’s with non-polar side chains force them to
face inward toward each other, away from the surrounding water. This leaves
polar amino acids facing outward into water.
DNA Contains Different Types of Genes
DNA contains different types of genes
• Protein coding: transcribe mRNA from DNA, translate protein synthesis from mRNA
• However, the total number of 20,000–25,000 protein-coding genes represent only 1.5% of total DNA
• Non-coding (nc): transcribe ncRNA, but do not translate proteins (will be covered later); 3% of genome
– Most human DNA codes for RNA transcription, but only a small subset also translate protein synthesis
– ncRNA bind to protein complexes at other sites and regulate genetic expression
• Regulatory: bind transcription regulator proteins ; do not transcribe RNA nor translate proteins; less than 2%
of genome
Protein Synthesis is Regulated…
Protein synthesis is regulated
• internally by transcription
factors
• externally by signaling factors
Protein Coding Genes
- What sort of proteins bind at protein coding genes? What are the promoter and the TATA box? What is the function of RNA polymerase? Is mRNA transcribed at all genes?
- What sort of proteins bind at protein coding genes? What are the promoter and the TATA box? What is the function of RNA polymerase? Is mRNA transcribed at all genes?
PROTEIN CODING GENES
Protein synthesis begins with assembly of RNA
transcription proteins at promoter region, which includes
the TATA site
Various proteins “dog pile” into a transcription complex
and attach to the promoter region of DNA
• RNA polymerase
• Transcription factors
– assemble at promoters
• Transcription regulators
– activators and suppressors that attach to
regulatory genes distant from the promoter and
regulate transcription factors
Messenger RNA
MESSENGER RNA (mRNA)
• Transcription complex unravels DNA and uses one
strand at a time to transcribe code into mRNA
• mRNA is then used to translate the code into
protein synthesis
Transcription & mRNA
DNA
Exons
Introns
DNA Consists of
Exons - useful regions
Introns -not useful regions
Only DNA exons are ultimately transcribed and translated. Introns are coded into mRNA and then spliced out.
Transfer RNA (tRNA)
- What is tRNA? What is the anti-codon and what does it bind to? How do tRNA’s bind to specific amino acids?
Transfer RNA (tRNA)
- What is tRNA? What is the anti-codon and what does it bind to? How do tRNA’s bind to specific amino acids?
tRNAs are transcribed from other genes
tRNA have anti-codons, nucleotide triplets that bind to codons, a set of complementary bases on the mRNA.
The RNA base sequence complementary to the anticodon on the opposite end of tRNA binds specific amino acids.
Transfer RNA (tRNA)
- What is tRNA? What is the anti-codon and what does it bind to? How do tRNA’s bind to specific amino acids?
Transfer RNA (tRNA)
- What is tRNA? What is the anti-codon and what does it bind to? How do tRNA’s bind to specific amino acids?
tRNAs are transcribed from other genes
tRNA have anti-codons, nucleotide triplets that bind to codons, a set of complementary bases on the mRNA.
The RNA base sequence complementary to the anticodon on the opposite end of tRNA binds specific amino acids.
Transcription & Translation
Transcription & Translation
Both mRNA and tRNA exit the nucleus via pores
Combine with ribosomes in cytosol
Ribosomes
- Describe protein translation by the ribosome and tRNA. Where does it occur? Nucleus? Rough ER?
RIBOSOMES
Ribosomes organize tRNA and mRNA to
translate DNA code into protein synthesis
• Consist of protein & ribosomal RNA
(rRNA)
• tRNA-AA complexes link with ribosomes
• Specific tRNA anticodons attach to
codons of mRNA
• Ribosome move along mRNA translating
the nucleotide sequence into an amino
acid sequence
• tRNA transfers a specific amino acid to a
growing polypeptide chain at ribosome
>>
Protein synthesis and translocation: two paths
- Proteins synthesized and inserted into rER: If synthesizing polypeptides destined for endomembrane system or for export from cell. >Cotranslational import
- Protein synthesized free in cytosol - If synthesizing polypeptides destined for the cytosol or for the mitochondria, chloroplasts,or peroxisomes. >Posttranslational import.
messenger RNA (mRNA) & Ribosomes
messenger RNA (mRNA) & Ribosomes
Several ribosomes generate
proteins along a single mRNA
Protein synthesis and translocation:
RIBOSOMES
Ribosomes organize tRNA and mRNA to
translate DNA code into protein synthesis
• Consist of protein & ribosomal RNA
(rRNA)
• tRNA-AA complexes link with ribosomes
• Specific tRNA anticodons attach to
codons of mRNA
• Ribosome move along mRNA translating
the nucleotide sequence into an amino
acid sequence
• tRNA transfers a specific amino acid to a
growing polypeptide chain at ribosome
>>
Protein synthesis and translocation: two paths
- Proteins synthesized and inserted into rER: If synthesizing polypeptides destined for endomembrane system or for export from cell. >Cotranslational import
- Protein synthesized free in cytosol - If synthesizing polypeptides destined for the cytosol or for the mitochondria, chloroplasts,or peroxisomes. >Posttranslational import.
Proteins synthesized in open cytosol
Proteins synthesized in open cytosol (i.e. not
inserted into rER) are transported to other
organelles
• Into nucleus via pores
• Into mitochondria and peroxisomes via
protein transporters
Protein synthesis on the ER
Protein synthesis on the ER
• If the protein the
ribosome is forming
contains an N-terminal
ER signal sequence, it
will be directed to the
ER membrane
• ER signal is cleaved off
by signal peptidase
after protein is inserted
into the ER
ER signal sequence on the
growing protein
ER signal sequence on the
growing protein directs the
ribosome to a translocator that
forms a pore through which the
protein is inserted.
• Signal sequence is cleaved
during translation by a
peptidase, and the remaining
protein is inserted into the
lumen of the ER
Protein insertion into rER
Protein insertion into rER
As proteins are synthesized, they are secreted into the rER lumen
In the rER, proteins are modified into glyco- or lipoproteins by resident enzymes.
Proteins inserted into
rER are then transported
within vesicles to form
Golgi apparatus
Protein insertion into rER
Protein insertion into rER
As proteins are synthesized, they are secreted into the rER lumen
In the rER, proteins are modified into glyco- or lipoproteins by resident enzymes.
Proteins inserted into
rER are then transported
within vesicles to form
Golgi apparatus
Golgi Apparatus
GOLGI APPARATUS
• Proteins transported
into rough endoplasmic
reticulum (rER) combine
with oligosaccharides
and lipids
• ER vesicles containing
proteins fuse to form Cis
Golgi layers
• Proteins are sorted into
types
• Trans Golgi releases
vesicles:
– Fuse to form
lysosomes
– Fuse with cell
membrane to insert
resident membrane
proteins
– Secrete proteins
into into the
extracellular space
Protein secretion
Protein secretion
• Golgi vesicles fuse with cell membrane and release contents by two mechanisms
• Unregulated mechanisms
– Proteins are inserted continually into the membrane or secreted from the cell
– Lipids from Golgi membrane are inserted into cell membrane
• Regulated mechanisms
– Proteins are secreted from the cell in response to extracellular signal (eg. pancreatic acinar cells)
Types of Protein synthesis include
• Types of proteins synthesized include, eg.
– Metabolic enzymes
– Histones (proteins around DNA)
– Transcription & regulatory factors
– Structural proteins
• Cell adhesion molecules (CAM)
• Receptors
• Ion channels
• Cytoskeleton
– Secreted proteins
• Extracellular matrix
• Signaling factors
Lipid synthesis
Areas of Protein function
Areas of protein functions we
will cover here are:
1. Enzymes
– Cellular energy is derived from
metabolism
– Proteins act as enzymes to facilitate
metabolic reactions
2. Differentiation
– Proteins are used as internal and
external signals to induce cell
division plus changes in structure
and function
Proteins as Enzymes
Proteins as Enzymes
• All cellular reactions require an activation energy to convert one
substrate into another
• What about just heating it?
• Enzymes lower the activation energ
Mechanisms that lower activation
• Mechanisms that lower activation
energy include
– proper orientation
– using charged groups to alter distribution of charges in substrate
– changing substrate shape
• Enzymes are very specific; they bind only to particular substrates
• Enzymes activity can be affected by
– Inhibitors such as drugs and poisons
– Activators such as other proteins
– Temperature, pH, substrate concentration
Enzymes often need coenzymes
Enzymes often need coenzymes
or cofactors to facilitate reactions
• Coenzymes can be metals or small molecules
ATP, Adenosine triphosphate
(same as in DNA)
• one of many examples of coenzymes
• has a high energy bond between the 2nd and 3rd
phosphate group used to drive energetically
unfavorable reaction
Energy for cell functions
Energy for cell functions, including protein synthesis,
comes from foodstuffs. Food is processed in
metabolism via two opposing streams of reactions
Catabolism
• Involves the breakdown of foodstuffs into intermediate products and ultimately CO2 & H2O and heat
• Catabolic pathways are energetically favorable and are facilitated by enzymes
• The intermediates created are used in synthesis of larger molecules (anabolism)
Anabolism:
• Synthesis of new molecular structures uses anabolic reactions which are energetically unfavorable.
• They require both enzymes & activated carrier molecules (eg. ATP) for energy
ATP is an activated carrier molecule produced by catabolic reactions:
• ATP is an activated carrier molecule produced by catabolic reactions:
– Energy from of foodstuffs ADP + P ATP
• ATP temporarily holds its energy so it can be used by anabolic reactions to build molecules: ATP ADP + P
– ATP is a coenzyme that helps enzymes construct patterns and structures with synthetic pathways
• Molecular synthesis increases the orderliness in cell organization (negative entropy).
– Entropy is a measure of disorderliness or dispersal of useful energy
• Development of orderliness and cellular structure is an example of self organization
- What sort of proteins bind at protein coding genes? What are the promoter and the TATA box? What is the function of RNA polymerase? Is mRNA transcribed at all genes?
PROTEIN CODING GENES
- What sort of proteins bind at protein coding genes? What are the promoter and the TATA box? What is the function of RNA polymerase? Is mRNA transcribed at all genes?
PROTEIN CODING GENES
Protein synthesis begins with assembly of RNA
transcription proteins at promoter region, which includes
the TATA site
Various proteins “dog pile” into a transcription complex
and attach to the promoter region of DNA
• RNA polymerase
• Transcription factors
– assemble at promoters
• Transcription regulators
– activators and suppressors that attach to
regulatory genes distant from the promoter and
regulate transcription factors
mRNA
MESSENGER RNA (mRNA)
• Transcription complex unravels DNA and uses one
strand at a time to transcribe code into mRNA
• mRNA is then used to translate the code into
protein synthesis
A living cell is an open, self organizing, dissipative structure, far from equilibrium
A living cell is an open, self organizing, dissipative structure, far from equilibrium
- Open systems permit influx and efflux of energy
- In open, self-organizing systems, the internal organization increases in complexity without being guided or managed by an outside source and typically display emergent properties.
– Complexity refers to the degree of emergent properties stemming from element interactions, not the total number of elements.
- Anabolic syntheses of complex structures or development patterns in gastrulation are emergent properties produced by the interaction of the elements of the system, eg. small molecules, enzymes, genes, etc.
- Interactions can be either direct or indirect, eg. if the behavior of one component modifies the environment and thus affects the behavior of another component.
Dissipative structure
2nd Law of Thermodynamics
Dissipative structure
2nd Law of Thermodynamics
•
Dissipative structure: The continuous flow of matter and energy and release of heat (dissipation) allows the system to self organize and exchange entropy with the environment
– Formation of structures within the cell creates and maintains the orderliness of the cell (decreases entropy) relative to the outside
– Heat released from these synthetic reactions decreases orderliness (increases entropy) outside the cell Second Law of Thermodynamics: Entropy of the universe increases
– With heat released from the cell, the increase in order (decreased entropy) internally is more than compensated by a greater decrease in order (increased entropy) externally.
Potential Energy & Entropy
A system that is “far from equilibrium “ contains potential energy, an energy capable of doing work.
- This is reflected in the higher level of negative entropy (orderliness) within the cell.
- Potential energy in a cell is partly due to the thousand-fold concentration gradient of ATP over ADP, created by metabolism in oxidative phosphorylation
– This could produce a significant release of energy for the cell
– At equilibrium, where ATP follows its energetically favorable path to ADP, and there are no uphill reactions creating negative entropy, ADP would exceed ATP. And the cell would be dead.
Hierarchy & Emergent Properties
The Bottom Line
- The same self-organizing principles seen in cells apply to the whole hierarchy from molecules to organism, within each level and among levels
- The interrelations among hierarchical levels produce emergent properties unpredicted by the properties of individual structural levels. This creates greater complexity as the hierarchical range increases. Grizzi F, et al. Theor Biol Med Model 2005, 2:26
- Organismal complexity is contingent on order, i.e. the synthesis of structures and their interrelations that reduces entropy relative to the external world
Regulation of Gene Expression
Regulation of Gene Expression
Determining which proteins are translated and how much is synthesized is regulated at many
possible steps between RNA transcription and protein translation. Two examples are:
• Regulation of mRNA transcription (1)
• Regulation of mRNA activity and protein translation (4,5)
Regulation of Gene Transcription & Transcription Factors
Regulation of Gene Transcription & Transcription Factors
TRANSCRIPTION FACTORS , TF
Proteins that BIND to promoter or regulatory regions of DNA
• General (basal) transcription factors (eg. TFIIA) bind to
either the promoter region or to the RNA polymerase and regulate
its activity
– Small number of them; will not be discussed further
• Gene regulatory proteins are transcription factors that bind
to regulatory genes and alter RNA transcription at the promoter
site
• I will call all of these Transcription Factors (TF)
Transcription Factors
Transcription factors TF
• Located throughout the cytoplasm and the
nucleus
• Activated and regulated by various other
factors (coregulators) such as local enzymes
(JNK/MAPK) and signaling from outside
sources
Most Transcription Factors are…
Most transcription factors (TF) are GENE REGULATORY PROTEINS that bind to REGULATORY GENES
– (other authors, eg. Alberts et al., call them just regulatory proteins or transcription regulators )
• Regulatory genes do not code for either RNA or protein; they only bind gene regulatory proteins
• TF are translated from 10% of the 25,000 genes that encode proteins
• TF Influence transcription rate of coding genes by regulating the following:
– Help position RNA polymerase
– Separate DNA strands to permit transcription
– Release RNA polymerase from promoter (TATA region) once transcription begins
• Regulatory genes provide fine control of differentiation and morphogenesis.
DNA Looping & TF
• DNA looping permits
contact between
regulatory TFs and other
TFs nearer to the promoter
• Regulatory TF also act as
DNA bending proteins
Regulatory Genes:
Enhancer
Silencer
Regulatory TF:
activators
repressors
Regulatory Genes:
Enhancer
Silencer
Regulatory TF:
activators
repressors
How do proteins “compete” with Transcription Factors?
Competition among activator and repressor regulatory proteins provides flexibility in both the direction (activate, suppress) and the overall degree of gene expression
What are homeotic genes? What are some examples of homeotic genes? What is the homeodomain?
SOURCE OF TRANSCRIPTION FACTORS Homeotic genes – encode TF that generate the body plan and organ development; several subtypes with specific functions
Hox genes encode TF that determine development of body
segmentation – Homeobox genes – subset of hox genes that encodes
the homeodomain sequence within TF protein that binds to regulatory genes in order to regulate patterns of gene expression
PAX6 produces TF for development of the eye Other homeotic genes include Sox, POU, Lim, T-Box, etc – all of which produce TF
- What is chromatin? What are histones and histone tails? What are nucleosomes? What is the difference between euchromatin and heterochromatin?
- What is chromatin? What are histones and histone tails? What are nucleosomes? What is the difference between euchromatin and heterochromatin?
- CHROMATIN REMODELING
AND HISTONE MODIFICATION Histone alteration regulates access of transcription factors and regulators to target genes
Histone structure • Most DNA is bound to histones and inaccessible to
transcription and regulatory factors • Nucleosomes consist of DNA wrapped around histone
octomers in two forms:
o Euchromatin
o Heterochromatin • TFs can reversibly interconvert eu- and
heterochromatin
- What is the difference between chromatin remodeling and histone modification?
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
In order to open the chromatin for access to DNA, transcription factors need to:
- Open chromatin by chromatin remodeling
- Label and subsequently identify which genes to bind to by modifying histone proteins
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
>>Chromatin Re-modeling
CHROMATIN REMODELING
Regulation of DNA-histone binding • DNA-histone coupling and decoupling can
occur spontaneously due to instability • DNA-binding proteins (chromatin remodeling complex) separate DNA from histones • TFs are accompanied by chromatin remodeling complexes (eg. SWI-SNF) that loosen DNA from histone • Thus, unwinding histones and binding TFs to DNA occur in the same step
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
>>Histone Modification
>Names of enzymes that do this!
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
>>Histone Modification
HISTONE MODIFICATION • methyl and acetyl groups bind
to histone “tails” OPEN CHROMATIN
- Acetylation by histone acetyl transferase (HAT)
- Trimethylation by methyl transferase
- Forms euchromatin and opens gene to TF binding
CLOSE CHROMATIN
- Methylation by methyl transferase
- Deacetylation by histone deacetylase (HDAC)
- Forms heterochromatin, closing the gene.
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
>>Histone Modification
>Names of enzymes that do this for acetyl groups?
- What is the difference between chromatin remodeling and histone modification? What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this?
>>Histone Modification
>Names of enzymes that do this!
Histone acetylation is directed by transcription factors
- In development, morphogens such as growth factors first recruit transcription factors (TF) in a large population of cells.
- TF approaches a gene combined with histone acetyl transferase (HAT) and other proteins
– TF-HAT open the gene for transcription
– HAT reconfigures the genes into a stable form by adding epigenetic acetyl tags to histone tails
• Type of epigenetic tag that marks which genes are available fro transcription
What is the transcriptional impact of single acetyl or methyl groups attached to histone tails? What are the names of the enzymes that do this? (for DNA methylation)
- DNA METHYLATION
CpG islands = DNA methylation site • Repeated cytosine-phosphate-
guanosine pairs • Occurs in 60% of gene promoters
DNA Methylation • Cytosines are methylated by DNA methyltransferases (DNMTs) • Usually SUPPRESSES gene expression (but can sometimes activate them)
• DNA methylation patterns essential for mammalian development and normal functioning in adulthood. Disturbed methylation sequences can lead to chronic illness, eg. cancer
DNA methylation is not universal
- methylation-resistant CGIs bind TFs that prevent methylation of house keeping genes that must remain open
- methylation-prone CGIs bind tissue– specific transcription factors
– associated with development, differentiation and cell communication
– facilitates histone deacetylation by HDACV (histone deacetylase)
– lead to formation of heterochromatin
- How does miRNA impact protein synthesis? Is it at the transcriptional or translational level?
- How does miRNA impact protein synthesis? Is it at the transcriptional or translational level?
Micro RNA (miRNA) see mRNA degradation control (4) on first slide
• •
Reduces translation of mRNA into proteins by degrading mRNA or blocking translation process
TF family determines which miRNAs are transcribed and hence determines which proteins are diminished. Lack of miRNA will permit more expression of another type of protein (yin-yang).
FYI: Several miRNAs are directly involved in lung, breast, brain, liver, colon cancer, and leukemia
- miRNAs operate by either cleaving mRNA or inhibiting translation in concert with RISC (RNA-induced silencing complex).
- Overexpression of miRNAs—for instance, by amplification of the miRNA-encoding locus—could decrease expression of the target, such as a tumor suppressor gene.
- Underexpression of miRNAs—for instance, by deletion or methylation of the miRNA locus—could result in increased expression of a target such as an oncogene.
- Describe DNA methylation in terms of: where does it occur? What enzymes are involved? What impact it has on gene transcription? How does it compare to other factors in determining the stability of gene transcription?
- Describe DNA methylation in terms of: where does it occur? What enzymes are involved? What impact it has on gene transcription? How does it compare to other factors in determining the stability of gene transcription?
- DNA METHYLATION
CpG islands = DNA methylation site • Repeated cytosine-phosphate-
guanosine pairs • Occurs in 60% of gene promoters
DNA Methylation • Cytosines are methylated by DNA methyltransferases (DNMTs) • Usually SUPPRESSES gene expression (but can sometimes activate them)
• DNA methylation patterns essential for mammalian development and normal functioning in adulthood. Disturbed methylation sequences can lead to chronic illness, eg. cancer
- How are the epigenetic markers maintained through the cell cycle? What is cell memory?
- How are the epigenetic markers maintained through the cell cycle? What is cell memory?
Maintenance of the epigenome during cell division
• Cell division propagates epigenetic code by maintaining the epigenetic tags on DNA and histones.
Cell memory - Maintenance of epigenetic code
Maintenance of the Epigenetic code
- Identifies which genes will be expressed and what type of a cell it will be.
- How are epigenetic tags maintained across many generations of cell division?
Cell cycle of mitosis
- GO, the resting state, can be interrupted by a stimulus that elicits cell division
- G1, the cell manufactures all the proteins and RNA to produce a new cell and a duplicate set of DNA
- S, duplication of the DNA takes 6-8 hours. This is also where epigenetic codes are
duplicated
• G2, the cell manufactures all the structural elements that the duplicate cell will need.
- What is meant by asymmetric division?
- What is meant by asymmetric division?
Asymmetric division
- Earliest developmental stages: asymmetric distributions of transcription factors in the cytoplasm
- During mitosis, TFs are divided unequally and produces cells with different patterns of gene expression
- How do signaling factors induce differentiation between two offspring cell?
- How do signaling factors induce differentiation between two offspring cell?
Induction by signaling factors
- Signaling factors specify patterns of gene expression of TF and epigenetic markers
- Concentration gradients of signaling factors determine the degree of differentiation
- Dominant mechanism of differentiation throughout development
- Positive feedback interaction between cells or intracellular transcription factors enhances difference between cells – lateral inhibition
- Describe what is meant by: signaling factor, receptor, signal transduction.
- Describe what is meant by: signaling factor, receptor, signal transduction.
OVERVIEW OF SIGNALING FACTORS AND THE CELL SIGNALING SYSTEM
Signaling factors
• Include: growth factors, peptides (eg. insulin, glucagon) & proteins, epinephrine, acetylcholine, histamine, ATP, steroid and thyroid hormones, prostaglandins, nitric oxide (NO)
Receptors
• Membrane bound or intracellular proteins that bind signaling factors
Signal transduction
• •
Chemical messages conveyed from receptors regulate TF activity on gene expression
Changes in gene expression regulate level of cell activity
– Up regulation: increased cell function – Down regulation: decreased cell function
Be able to recognize the major families of growth factors.
Be able to recognize the major families of growth factors.
Growth factor is a specific type of signaling factor necessary for cell growth and development
Families of growth factors • TGF (transforming growth factor)
– tissue regeneration, cell differentiation, embryonic development and regulation of the immune system
• FGF (fibroblast growth factor)
– Development of mesoderm , limb and neural development; regulation of angiogenesis, keratinocyte organization, and wound healing in adult tissue
• Wnt – wingless types • Hedgehogs (Sonic, desert, Indian,
tiggy-winkle)
– Regulates embryonic development of digits on limbs and the brain, plus cell division of adult stem cells
- Be able to give a general and brief description of how miRNA interacts with epigenetic markers of DNA and histones.
- Be able to give a general and brief description of how miRNA interacts with epigenetic markers of DNA and histones.
Role of miRNA in differentiation • Recall how TF families determine the types of miRNA transcribed and how they constrain the number
of mRNA’s that will be translated into protein • miRNAs facilitate transitions in development by reducing protein production from mRNAs inherited
from an earlier developmental stage
miRNA and epigenetic mechanisms form a mutually inhibiting control system
• miRNAs control the relative expression of DNA methyltransferases and histone deacetylases thereby determining the amount of gene product
• DNA methylation and histone modification in turn regulate the expression of miRNAs. • Disruption of the circuit can contribute to various disease processes.
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? How do morphogen concentration gradients impact pattern formation?
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition?
MORPHOGENESIS Development of tissue/organ form and
shape that involves 1. Morphogens: signaling factors that
act on a population of cells
- Changes in spatial distribution of cells (i.e. environment) due to morphogenetic mechanisms including:
– Lateral inhibition – Differential adhesion – Cell polarity – Morphogen gradient – Segmentation
Morphogenesis involves a change in scale from individual cells to multicellular populations
LATERAL INHIBITION
- Early differentiating cells signal to adjacent cells to become something different
- Asymmetric division creates a lead cell which in turn inhibits differentiation of neighboring cells by the Notch-Delta pathway
- Process of self organization that produces heterogeneous cell populations in structural development as well as functional specialization in post natal life
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? II
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition?
MORPHOGENESIS Development of tissue/organ form and
shape that involves 1. Morphogens: signaling factors that
act on a population of cells
- Changes in spatial distribution of cells (i.e. environment) due to morphogenetic mechanisms including:
– Lateral inhibition – Differential adhesion – Cell polarity – Morphogen gradient – Segmentation
Morphogenesis involves a change in scale from individual cells to multicellular populations
LATERAL INHIBITION
- Early differentiating cells signal to adjacent cells to become something different
- Asymmetric division creates a lead cell which in turn inhibits differentiation of neighboring cells by the Notch-Delta pathway
- Process of self organization that produces heterogeneous cell populations in structural development as well as functional specialization in post natal life
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? How do morphogen concentration gradients impact pattern formation?
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? How do morphogen concentration gradients impact pattern formation?
MORPHOGEN CONCENTRATION GRADIENTS
• •
•
Signaling factors spread by diffusion
Signal gradient determines the degree of impact on the target cell
Mutual inhibition
- Where does fertilization occur? Where does implantation occur? What stage implants in the uterus?
- Where does fertilization occur? Where does implantation occur? What stage implants in the uterus?
Fertilization occurs in the uterine tube. The blastocyst begins in implant in the uterine endometrium.
FIRST WEEK
• Fertilization
• Cleavage
• Morula
• Blastula
• Cavity (blastocoel): created by secretion of Na+ & water via Na-/K+ ATP-ase
• Blastocyst = blastula plus
– Inner cell mass (embryoblast)
– Trophoblast surface
- What is an ectopic implantation and where do they occur?
- What is an ectopic implantation and where do they occur?
An ectopic pregnancy, or eccysis, is a complication of pregnancy in which the embryo implants outside the uterine cavity.[1] With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the mother, since internal haemorrhage is a life-threatening complication. Most ectopic pregnancies occur in the Fallopian tube (so-called tubal pregnancies), but implantation can also occur in the cervix, ovaries, andabdomen. An ectopic pregnancy is a potential medical emergency, and, if not treated properly, can lead to death.
- What are the characteristics of the zygote, morula, blastula, blastocyst? And where are they found?
- What are the characteristics of the zygote, morula, blastula, blastocyst? And where are they found?
Zygote: A zygote (from Greek ζυγωτός zygōtos “joined” or “yoked”, from ζυγοῦνzygoun “to join” or “to yoke”),[1] is the initial cell formed when two gametecells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo. In single-celled organisms, the zygote divides to produce offspring, usually through mitosis, the process of cell division. Location: Uterine tube
Morula: A morula (Latin, morum: mulberry) is an embryo at an early stage ofembryonic development, consisting of cells (called blastomeres) in a solid ball contained within the zona pellucida.[1]. Location: uterine tube
Blastula: The blastula (from Greek βλαστός (blastos), meaning “sprout”) is a hollow sphere of cells, referred to as blastomeres, surrounding an inner fluid-filled cavity called the blastocoele formed during an early stage of embryonic development in animals.[1] Embryo development begins with a sperm fertilizing an egg to become a zygote which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoele is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.[2]. Location: Uterine cavity
Blastocyst: The blastocyst is a structure formed in the early development of mammals. It possesses an inner cell mass (ICM) which subsequently forms the embryo. The outer layer of the blastocyst consists of cells collectively called thetrophoblast. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. The trophoblast gives rise to the placenta.
In humans, blastocyst formation begins about 5 days after fertilization, when a fluid-filled cavity opens up in the morula, a ball consisting of a few dozen cells. The blastocyst has a diameter of about 0.1-0.2 mm and comprises 200-300 cells following rapid cleavage (cell division). After about 1 day, the blastocyst embeds itself into the endometrium of the uterine wall where it will undergo later developmental processes, including gastrulation.
- Describe the epigenetic changes that occur in the morula and blastula and what is their significance?
- Describe the epigenetic changes that occur in the morula and blastula and what is their significance? What is the significance of de novo methylation after implantation?
FIRST WEEK • Fertilization • Cleavage • Morula • Blastula
• Cavity (blastocoel): created by secretion of Na+ & water via Na-/K+ ATP-ase • Blastocyst = blastula plus
– Inner cell mass (embryoblast) – Trophoblast surface
Blastocyst formation[edit]
The morula, which precedes the blastocyst, is an early embryo composed of 16 undifferentiated cells. Shortly following the morula’s entry into the uterus from the Fallopian tube, the morula becomes the blastocyst through cellular differentiation and cavitation. The morula’s cells differentiate into two types: an inner cell mass growing on the interior of the blastocoel and trophoblast cells growing on the exterior.[2] The animal pole refers to the side of the blastocyst where the ICM resides, while the vegetal pole is on the opposite side. Cavitation is the process by which a fluid cavity forms inside the embryo. The trophoblast cells pump sodium ions into the center of the embryo, which causes water to enter through osmosis. This forms an internal fluid-filled cavity called the blastocoel. This distinguishable blastocoel cavity in addition to cellular specification are both hallmark identities of the blastocyst.[3]
Implantation[edit]
Implantation is critical to the survival and development of the early embryo. It establishes a connection between the mother and the early embryo which will continue through the remainder of the pregnancy. Implantation is made possible through structural changes in both the blastocyst and endometrial wall.[4] The zona pellucida surrounding the blastocyst breaches, referred to as hatching. This removes the constraint on the physical size of the embryonic mass and exposes the outer cells of the blastocyst to the interior of the uterus. Furthermore, hormonal changes in the mother, specifically a peak in luteinizing hormone (LH) prepares the endometrium to receive the blastocyst and envelope it. Once bound to the extracellular matrix of the endometrium, trophoblast cells secrete enzymes and other factors to embed the blastocyst into the uterine wall. The enzymes released degrade the endometrial lining, while autocrine growth factors such as human chorionic gonadotropin(hCG) and insulin-like growth factor (IGF) allow the blastocyst to further invade the endometrium.[5]
Implantation in the uterine wall allows for the next step in embryogenesis, gastrulation, which includes formation of the placenta from trophoblastic cells and differentiation of the ICM into the amniotic sac and epiblast.
- Describe the epigenetic changes that occur in the morula and blastula and what is their significance? What is the significance of de novo methylation after implantation?
- Describe the epigenetic changes that occur in the morula and blastula and what is their significance? What is the significance of de novo methylation after implantation?
Embryological DNA methylation and “Epigenetic reprogramming” begin in early stages
• Unmethylated primordial germ cell DNA become methylated as cells develop postnatally into sperm
or ova (gametogenesis)
• After fertilization, general demethylation of the maternal and paternal genomes continues until
implantation
• After implantation, de novo DNA methylation of specific genes that epigenetically determines cell
lineage = reprogramming
– How do they know this?
• Transgenerational epigenetic inheritance via “germ line differentially methylated regions” (gDMRs) =
imprinting from parents
- Describe how the epiblast and hypoblast arise. How are the amniotic cavity and yolk sac formed?
- Describe how the epiblast and hypoblast arise. How are the amniotic cavity and yolk sac formed?
SECOND WEEK
Inner cell mass divides into two
epithelial layers that form spaces
• Epiblast
– amniotic cavity
• Hypoblast (endoblast)
– yolk sac – primary and
secondary
Trophoblast -> placenta
Cavities:
• Amniotic
• Yolk sac
Becoming bilaminar[edit]
The zygote first transformed into a morula through cleavage and then more divisions lead to a blastocyst that consisted of just a trophoblast, and an embryoblast. By the end of the first week, the embryoblast has begun separating into two layers: the epiblast and hypoblast also called the primitive endoderm. At the embryonic pole of the blastocyst, the amniotic cavityfinds a home between the epiblast and the hypoblast. The epiblast stretches to surround the cavity very quickly and this layer of the epiblast becomes known as the amnion, which is one of the four extraembryonic membranes. The rest of thehypoblast and epiblast, not including the amnion, is what contributes to the bilaminar embryonic disc (bilaminar blastoderm/blastocyst), which sits between the amniotic cavity and the blastocyst cavity. The embryo proper and extramembryonic membranes are later derived from the embryonic disc.[3]
Establishment of the amniotic cavity[edit]
Beginning on day 8, the amniotic cavity is the first new cavity to form during the second week of development.[3] Fluid collects between the epiblast and the hypoblast, which splits the epiblast into two portions. The layer at the embryonic pole grows around the amniotic cavity, creating a barrier from the cytotrophoblast. This becomes known as the amnion, which is one of the four extraembyonic membranes and the cells it comprises are referred to as amnioblasts.[5] Although, theamniotic cavity starts off small it eventually grows to be larger than the blastocyst and by week 8, the whole embryo is encompassed by the amnion.[3]
Yolk sac during development[edit]
Like the amnion, the yolk sac is simply an extraembryonic membrane that surrounds a cavity. Formation of the definitiveyolk sac happens after the extraembryonic mesoderm splits, and it becomes a double layered structure with hypoblast-derived endoderm on the inside and mesoderm surrounding the outside. The definitive yolk sac contributes greatly to the embryo during the 4th week of development and it executes critical functions for the embryo. One of which being the formation of blood, or hematopoiesis. Also, Primordial germ cells are first found in the wall of the yolk sac. After the 4th week of development, the growing embryonic disc becomes a great deal larger than the yolk sac and its presence usually dies out before birth. However, seldom will the yolk sac remain as deviation of the digestive tract named Meckel’s diverticulum.[3]
- What is the fate of the epiblast? The hypoblast?
- What is the fate of the epiblast? The hypoblast?
Inner cell mass divides into two epithelial layers that form spaces • Epiblast
– amniotic cavity • Hypoblast (endoblast)
– yolk sac – primary and secondary
Trophoblast -> placenta
Cavities: • Amniotic • Yolk sac
THIRD WEEK
• Gastrulation
• Notochord formation
• Neurulation
GASTRULATION is the
formation of the three germ
layers
• Midline epiblast cells differentiate,
separate, migrate and form the
mesoderm and endoderm layers
Epiblast cells during gastrulation[edit]
The third week of development and the formation of the primitive streak sparks the beginning of gastrulation.[3] Gastrulationis when the three germ cell layers develop as well as an organism’s body plan.[6] During gastrulation, cells of the epiblast, a layer of the bilaminar blastocyst, migrate towards the primitive streak, enter it, and then move apart from it through a process called ingression.[3]
Definitive endoderm development[edit]
On day 16, epiblast cells that are next to the primitive streak experience epithelial-to-mesenchymal transformation as they ingress through the primitive streak. The first wave of epiblast cells takes over the hypoblast, which slowly becomes replaced by new cells that eventually constitute the definitive endoderm. The definitive endoderm is what makes the lining of the gut and other associated gut structures.[3]
–
Overview[edit]
In amniotes, gastrulation occurs in the following sequence: (1) the embryo becomes asymmetric; (2) the primitive streakforms; (3) cells from the epiblast at the primitive streak undergo an epithelial to mesenchymal transition and ingress at theprimitive streak to form the germ layers.[4]
- Describe how the three germ layers are formed in gastrulation
- Describe how the three germ layers are formed in gastrulation
THIRD WEEK
• Gastrulation
• Notochord formation
• Neurulation
GASTRULATION is the
formation of the three germ
layers
• Midline epiblast cells differentiate,
separate, migrate and form the
mesoderm and endoderm layers
–
Endoderm and mesoderm formed in two phases
• Formation of endoderm and fate of hypoblast
• Formation of mesoderm
Remaining epiblast becomes ectoderm and
notochord
Three layer embryo :
ECTODERM
MESODERM
ENDODERM
- What is the epithelial-mesenchymal transition?
- What is the epithelial-mesenchymal transition?
TISSUE DIFFERENTIATION BY EMT AND ITS REVERSIBILITY
• Mesenchymal cells migrate away from epiblast and re-aggregate into secondary epithelium
• Secondary epithelium either remains epithelium or differentiates into various types of CT via
EMT. Transcription factors are indicated.
• In adult stage, secondary epithelia can transform into tumors that undergo EMT to
metastasize. Also, renal tubules can change from epithelium into CT to generate FIBROSIS of
the kidney.TISSUE DIFFERENTIATION BY EMT AND ITS REVERSIBILITY
• Mesenchymal cells migrate away from epiblast and re-aggregate into secondary epithelium
• Secondary epithelium either remains epithelium or differentiates into various types of CT via
EMT. Transcription factors are indicated.
• In adult stage, secondary epithelia can transform into tumors that undergo EMT to
metastasize. Also, renal tubules can change from epithelium into CT to generate FIBROSIS of
the kidney.
- Be able to recognize which general structures arise from the three germ layers.
- Be able to recognize which general structures arise from the three germ layers.
ECTODERM gives rise to brain and
external
layer of body, the skin
• Central nervous system, CNS
– Brain & spinal cord; glia
• Neural crest
– Peripheral nervous system, PNS
– Dermal pigmented cells
– Bone & CT of face/neck
• Epidermis, hair, nails, teeth enamel, etc
MESODERM gives rise to middle level
structures such as muscle & connective tissue
• Connective Tissue: bone, cartilage, CT,
blood
• Muscle: striate, smooth, cardiac
• Glands: kidney, gonads, adrenal cortex
• Pleura, pericardium, peritoneum
ENDODERM gives rise to the deep level
structures of the gut tube and its derivatives
• GI, Liver, pancreas
• Lungs
• Bladder/urethra
- Where is the notochord and how does it impact the development of the nervous system? What signaling factor is involved?
- Where is the notochord and how does it impact the development of the nervous system? What signaling factor is involved?
Notochord
• Forms within
mesoderm
• Induces formation
of CNS and
somites.
• Differentiation
into nucleus
pulposus
Sonic hedgehog (Shh)
• Notochord signaling molecule that activates TF in neural plate
• Morphogenetic cylinder formation
• Contraction of actin filaments in apical region of polarized cell
- What are the morphogenetic steps that generate the cylinder that will form the central nervous system? What are some of the peculiar fates of neural crest cells? I
- What are the morphogenetic steps that generate the cylinder that will form the central nervous system? What are some of the peculiar fates of neural crest cells?
ECTODERM gives rise to brain and
external
layer of body, the skin
• Central nervous system, CNS
– Brain & spinal cord; glia
• Neural crest
– Peripheral nervous system, PNS
– Dermal pigmented cells
– Bone & CT of face/neck
• Epidermis, hair, nails, teeth enamel, etc
–
Neurulation
• Neural tube created by fusion of neural folds,
bordering the neural groove.
• Neural crest pluripotent cells migrate
Neural crest cells migrate into
mesoderm to form:
• Peripheral nervous system: sensory
neurons, glia, autonomic postganglionic
cells including adrenal medulla and
enteric nervous system in the gut.
• Pigmented skin cells, skull bones, etc
- What are the morphogenetic steps that generate the cylinder that will form the central nervous system? What are some of the peculiar fates of neural crest cells? II
- What are the morphogenetic steps that generate the cylinder that will form the central nervous system? What are some of the peculiar fates of neural crest cells? II
Notochord
• Forms within
mesoderm
• Induces formation
of CNS and
somites.
• Differentiation
into nucleus
pulposus
- Describe how food deprivation during early embryogenesis can impact levels of gene methylation, such as IGF2? Would folate supplementation be a good idea in early pregnancy if you suspect a mother was not eating right?
- Describe how food deprivation during early embryogenesis can impact levels of gene methylation, such as IGF2? Would folate supplementation be a good idea in early pregnancy if you suspect a mother was not eating right?
Epigenetic impact of the Dutch Hunger Winter
• Individuals who were prenatally exposed to
famine during the Dutch Hunger Winter in
1944–45 had, 60 years later, hypomethylation
of IGF2 (a maternally imprinted gene
implicated in growth and development)
compared with their unexposed, same-sex
siblings.
• The association was specific for
periconceptional (but not late gestational)
exposure, thus very early development is a
crucial period for establishing epigenetic
marks that persist throughout life.
• F1 famine exposure in utero was associated
with increased F2 neonatal adiposity and poor
health in later life implying that the increase
in chronic disease after famine exposure in
utero is not limited to the F1 generation but
persists in the F2 generation.
A typical daily ration distributed by the local
authorities in the famine-struck western part
of the Netherlands consisted of two slices of
bread, two potatoes and piece of sugar beet.
The newspaper in the background announces
the closure of the soup kitchens.
Hypomethylation may be related to a deficiency in methyl
donors, such as the amino acid methionine, folate, etc.
• In sheep, offspring with periconceptional B vitamin and
methionine restricted diet, 4% of 1,400 CpG sites had
altered methylation and numerous phenotypic alterations,
such as increased body mass, altered immune responses to
antigenic challenge, insulin resistance, and elevated blood
pressure.
Predictive adaptive response
• Poor maternal nutrition may signal to the fetus that
nutrients are scarce; the fetus may then adapt its
metabolism to conserve energy demands, increase its
propensity to store fat and accelerate puberty.
• If the epigenetic prediction is correct (poor nutrition), the
metabolism of the organism will be matched to the
environment and have a low risk of disease.
If the prediction is incorrect and the offspring is
mismatched with the environment (over nutrition), then it
is at risk of metabolic disease: Insulin resistance, central
fat deposition, etc. This phenotype is advantageous in a
food deprived environment, because it conserves
resources via reduced growth, and diverts substrate from
metabolism to fat deposition to provide energy stores. The
phenotype is highly appropriate to any mammal with
restricted food supply See Gluckman and Hanson on
PubMed for more studies, esp
Adaptive value of epigenetically
transmitted familial susceptibility
to cardiovascular disease, obesity
and other non-communicable
diseases
What are the “regulatory proteins”?
What are the “regulatory proteins”?
Examples include Activators & Repressors (and they bind to regulatory genes :)
How do signaling factors induce differentiation between 2 offspring cell?
How do signaling factors induce differentiation between 2 offspring cell?
Signaling factors differentiate between 2 offspring cells since they create different TFs that create different genes.
How do TF ensure that they are the primary or dominant factors that determine which genes will be expressed?
How do TF ensure that they are the primary or dominant factors that determine which genes will be expressed?
TFs go down the DNA strand and recognize/detect where coding genes are.
- What are the primary pathways the signaling factors use in reaching their target cells? Which ones are more likely to be used in an embryo consisting of only a few hundred cells?
- What are the primary pathways the signaling factors use in reaching their target cells? Which ones are more likely to be used in an embryo consisting of only a few hundred cells?
Signaling factors communicate
from one cell to another in various
ways. Some examples:
1. Endocrine: transport through
circulatory system
• peptides (eg. insulin, glucagon)
& proteins, epinephrine,
steroid and thyroid hormones
2. Paracrine: diffuse from cell to cell
through the extracellular fluid
• Growth factors (FGF),
histamine, nitric oxide (NO),
ATP
3. Neuronal: move across synapse
• Acetylcholine, norepinephrine
4. Contact dependent: cell surface
molecule (signaling factor)
binds to receptor molecule on
adjacent cell
• Delta
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? How do morphogen concentration gradients impact pattern formation?
- What is morphogenesis? Be able to recognize the different ways that cells interact to generate body forms and structures. What is lateral inhibition? How do morphogen concentration gradients impact pattern formation?
Even if it’s the same signaling factor, the amount of signaling factor can determine what muscle or organ will be formed.
- Describe what happens to the following during the folding of the embryo: amniotic cavity, yolk sac, intraembryonic coelom,
- Describe what happens to the following during the folding of the embryo: amniotic cavity, yolk sac, intraembryonic coelom.
The amniotic cavity gets pulled to the sides, stretched out and then eventually disappears. The intraembryonic coelem becomes the bursae and allows the guts to rub against each other, and the yolk sack becomes the lining of the digestive track.
- Briefly describe the differences among the four types of tissues.
- Briefly describe the differences among the four types of tissues.
Despite the body’s complexity, there are only 4 type of
tissues:
• Epithelium
• Interconnected cells
• Functions
• Connective tissue (CT)
• Constituents: cells, matrix (ground substance &
collagen)
• Types & Functions
• Nerve
• Cell types
• Communication
• Muscle
• Function & types
• Similarity to nerve
- Compare and contrast the properties of the following cell junctions: occluding, adhering, communicating
- Compare and contrast the properties of the following cell junctions: occluding, adhering, communicating
TIGHT (or OCCLUDING) JUNCTIONS
(Zonula occludens)
• Nearest to apex
• Diffusion barrier: impermeable to large molecules,
variably permeable to water and ions
• Maintains polarity of cell constituents
• Claudin determines permeability to water and other
molecules
ADHERING JUNCTIONS - Zonula adherens and
macula adherens, i.e. DESMOSOME
• Interconnect epithelial cells
• Cadherin:
• Adhesion between cells; resists physical
disruption
• Connect to intracellular actin; intracellular
communication
GAP (COMMUNICATING) JUNCTIONS
• Channels permit direct passage of
signaling molecules and ionic current
between cells
• Connexons
- What is the basement membrane and how does it differ from basal lamina? Where do you find basement membranes?
- What is the basement membrane and how does it differ from basal lamina? Where do you find basement membranes?
Basal Domain
BASEMENT MEMBRANE – Protein filled layer between epithelium and CT
• Basal lamina
• thin, acellular layer of proteins eg. integrin, laminin (a glycoprotein)
secreted by the epithelial cells
• forms flexible layer that supports overlying epithelium
• barrier for transport of substances between blood and cells
• Reticular lamina
• layer of collagens secreted by underlying CT
• connects epithelium and the basal lamina to underlying CT
B
- What are microvilli and how do they compare to cilia? What is the role of cilia in respiratory epithelium?
- What are microvilli and how do they compare to cilia? What is the role of cilia in respiratory epithelium?
APICAL DOMAIN
Microvilli
• Brush border
• Increase surface area; actin
interacts with myosin II to
adjust microvilli length and
rigidity
Stereocilia (not shown)
• Microvilli of unusual length
found in only a few tissues:
epididymis, ductus deferens,
sensory cells of ear
Cilia
• Microtubules
derived from basal
body
• Movement:
dyneins form cross
bridges on
microtubules,
bending the cilia
- What are the types and some examples of simple epithelium? What is pseudostratified epithelium?
- What are the types and some examples of simple epithelium? What is pseudostratified epithelium?
EPITHELIAL TYPES
Simple & stratified
SIMPLE
1. Simple squamous
epithelium
- Simple
cuboidal
epithelium - Simple
columnar
epithelium - Pseudostratified
• Appears multiply layered, but is a single layer of cells.
• Ciliated and non-ciliated forms
EX: Respiratory epithelium is pseudostratified
- What are the types and some examples of stratified epithelium?
- What are the types and some examples of stratified epithelium?
STRATIFIED
EPITHELIUM
1. Stratified squamous
• Keratinized, eg.
skin
- Stratified
squamous
• non-keratinized
• Eg. lining of
mouth,
esophagus - Stratified cuboidal
• Glandular ducts, eg sweat gland - Stratified columnar
• Glandular ducts, eg mucus gland duct in tongue - Transitional
• Expandable type of stratified
• bladder
- What are the basic constituents of CT? What are the types of “proper” CT?
- What are the basic constituents of CT? What are the types of “proper” CT?
CONNECTIVE TISSUE, CT
Cells
Extracellular matrix
Fibers
Ground substance
CT CELLS
Those derived from mesenchyme:
• Fibroblasts
• Adipocytes
• Mesenchymal stem cells
• Some remain in adult tissue
to become myofibroblasts
during wound healing. They
have characteristics of both
fibroblast and smooth
muscle cell types and can
contract
EXTRACELLULAR
MATRIX, ECM
• Fibers
• Ground Substance
COLLAGEN FIBERS
• Flexible, strong glycoprotein fibers
• Helical α chains form collagen fibrils
• CT turnover, collagen is degraded by
• Matrix metalloproteinases (MMPs)
• Phagocytosis by fibroblasts and
macrophages
CONNECTIVE
TISSUE TYPES
• CT proper
Loose (areolar) CT
Reticular, elastic
Adipose
Dense - regular & irregular
• Special CT (seen in other
lectures)
Blood
Cartilage
Bone
- Compare loose with dense CT. Compare regular and irregular CT.
- Compare loose with dense CT. Compare regular and irregular CT.
Loose CT
• Contains various cells, type 1 collagen fibers, abundant ground
substance, deep to skin, epithelia
• Viscous gel-like consistency
• Diffusion of O2
, CO2
and nutrients
Dense CT
• Higher concentration of type I collagen compared to loose CT
Irregular dense CT:
• collagen bundles are oriented in various directions, eg.
submucosa in the GI tract
Regular dense CT Picture: Left is irregular, right is regular)
• collagen bundles are densely arranged in
parallel, eg. tendons, ligaments
- What type of cells are found in CT? What do they do?
- What type of cells are found in CT? What do they do?
• Connective tissue (CT)
• Constituents: cells, matrix (ground substance &
collagen)
• Types & Functions
CT CELLS
Those derived from mesenchyme:
• Fibroblasts
• Adipocytes
• Mesenchymal stem cells
• Some remain in adult tissue
to become myofibroblasts
during wound healing. They
have characteristics of both
fibroblast and smooth
muscle cell types and can
contract
- In the ECM, what is collagen? What is elastic CT and how does it compare to loose and reticular CT?
- In the ECM, what is collagen? What is elastic CT and how does it compare to loose and reticular CT?
EXTRACELLULAR
MATRIX, ECM
• Fibers
• Ground Substance
COLLAGEN FIBERS
• Flexible, strong glycoprotein fibers
• Helical α chains form collagen fibrils
• CT turnover, collagen is degraded by
• Matrix metalloproteinases (MMPs)
• Phagocytosis by fibroblasts and
macrophages
Elasticity
• Elastic fibers enable many types of CT to snap back with stretch
• Hydrophobic elastin uncoils and recoils with stretch up to 1.5
times their length
• In matrix of CT (skin, nuchal lig), cartilage (ear, nose, larynx,
auditory tube), bronchial tree, blood vessel smooth muscle
• Elastic fibers function without replacement throughout lifetime
• Half-lives of types I and II collagen in human skin, articular
cartilage and intervertebral disc are 15, 95 and 117 years
• Elastin degraded MMP in age-related inflammatory conditions:
emphysema, atherosclerosis, excess UV exposure, etc
Reticular CT
• Type III collagen fibers: thin, unbundled, flexibility
• Holds together the parenchyma of various organs:
liver, kidney, spleen, lymph nodes, bone marrow and
adipose tissue
Loose CT
• Contains various cells, type 1 collagen fibers, abundant ground
substance, deep to skin, epithelia
• Viscous gel-like consistency
• Diffusion of O2
, CO2
and nutrients
- Describe the constituents of ground substance. What are glycosaminoglycans? Proteoglycans? What is hyaluronic acid? What does it do?
- Describe the constituents of ground substance. What are glycosaminoglycans? Proteoglycans? What is hyaluronic acid? What does it do?
GROUND SUBSTANCE
• Viscous, high water content,
• Consists of mainly:
Glycosaminoglycans GAG
• Polysaccharide chains: attract water
• Proteoglycans: GAG attached to proteins
• Transported into the ECM
• Repeating disaccharides of different types
yield various forms of GAG: chondroitin,
dermatan, etc
Proteoglycans attach to:
• Collagen fibers
• Hyaluronan
• Cell membranes
Hyaluronan (hyaluronic acid)
• Large GAG formed on the exterior surface
of the cell membrane
• Attracts water to form hydrated gel
• Provides ECM rigidity to resist
compression and provide structural
integrity of matrix
