Chap 1 Flashcards
Embryonic development is directed by?
Genomes
There are approximately how many genes in a human genome?
23000
Enumerate the 4 levels where gene expression can be regulated
- Different genes may be transcribed
- DNA transcribed from a gene may be selectively processed to regulate which RNAs reach the cytoplasm to become messenger RNAs (mRNAs)
- mRNAs may be selectively translated
- Proteins made from the mRNAs may be differentially modified
A complex of DNA and proteins
Chromatin
Basic unit structure of chromatin
Nucleosome
Each nucleosome is composed of an octamer of
Histone proteins and approximately 140 base pairs of DNA
What keeps the DNA tightly coiled such that it cannot be transcribed
Nucleosomes
In this inactive state, chromatin appears as beads of nucleosomes on a string of DNA and is referred to as?
Heterochromatin
For transcription to occur, this DNA must be uncoiled from the beads. In this uncoiled state, chromatin is referred to as?
Euchromatin
Genes reside within the DNA strand and contain regions called? They can also be translated into proteins
Exons
These are interspersed between exons and which are not transcribed into proteins
Introns
This binds RNA polymerase for the initiation of transcription, a translation initiation site, a translation termination codon and a , 3’ untranslated region
Promoter region
The promoter region is upstream or downstream?
Upstream from the transcription initiation site
In order to bind to the TATA box the polymerase requires additional proteins called
Transcription factors
In combination with other proteins, transcription factors does what?
Activate gene expression by causing the DNA nucleosome complex to unwind, by releasing the polymerase do that it can transcribe the DNA template, and by preventing new nucleosomes from forming.
Are regulatory elements of DNA that activate utilization of promoters to control their efficiency and the rate of transcription from the promoter.
Enhancers
They bind transcription factors and are used to regulate the timing of a genes expression and it’s cell specific location
Enhancers
The PAX6 transcription factor participates in
Pancreas, eye, and neural tube development
The PAX6 transcription factor contains how many enhancers?
Three enhancers each of which regulates the genes expression in the appropriate tissue.
Enhancers act by
Altering chromatin to expose the promoter or by facilitating binding of the RNA polymerase.
Enhancers that inhibit transcription are called?
Silencers
A silencer of genes
Methylation of cytosine bases
DNA methylation is also responsible for
Genomic imprinting
Explain genomic imprinting
Where only a gene inherited from the father or mother is expressed, whereas the other gene is silenced.
Methylation silences DNA by
Inhibiting binding of transcription factors or by altering histone binding resulting in stabilization of nucleosomes and tightly coiled DNA that cannot be transcribed.
The initial transcript of gene is called
Nuclear RNA or premessenger RNA
Why is nRNA longer than mRNA?
Because it contains introns that are removed (spliced out) as the nRNA moves from the nucleus to the cystoplasm.
Alternative splicing is
When cells produce different proteins from a single gene. Example, by removing different introns, exons are spliced in different patterns. This process is carried out by spliceosomes which are complexes of small nuclear RNAs
Proteins derived from the same gene are called
Splicing isoforms also called splice variants or alternative splice forms. These afford the opportunity for diff cells to use the same gene to make proteins specific for that cell type. Example, isoforms of the WT1 gene have different functions in gonadal versus kidney development.
How are organs formed?
By interactions between cells and tissues. Most often one group of cells or tissues causes another set of cells or tissues to change their fate by a process called INDUCTION.
The capacity to respond to a signal is called
Competence
Competence requires activation of the responding tissue by
A compatence factor.
Give examples of epithelial-mesenchymal ineractions
- Gut endoderm and surrounding mesenchyme to produce gut derived organs, including the liver and pancreas.
- Limb mesenchyme with overlying ectoderm (epithelium) to produce limb outgrowth and differentiation.
- Endoderm of the ureteric bud and mesenchyme from the metanephric blastema to produce nephrons in the kidney.
This is essential for induction, for conference of competency to respond, and for crosstalk between inducing and responding cells.
Cell to cell signalling
Whereby proteins synthesized by one cell diffuse over short distances to interact with other cells
Paracrine interaction
Doe not involve diffusible proteins
Juxtacrine signalling
Diffusable proteins responsible for paracrine signalling are called
Paracrine factors or growth and differentiation factors (GDF)
By activating a pathway directly or by blocking the activity of an inhibitor of a pathway, paracrine factors act by
Signal transduction pathways
Signal transduction pathways include a
Signaling molecule and a receptor
The receptor spans the cell membrane and has an
Extracellular domain, a transmembrane domain, and a cytoplasmic domain.
General pathway of signal transduction
- When a ligand binds it’s receptor, it induces a conformational change in the receptor that activates it’s cytoplasmic domain.
- The results of this activation is to confer enzymatic activity to the receptor, and most often this activity is a kinase that can phosphorylate other proteins using ATP as a substrate.
- In turn, phosphorylation activates these proteins to phosphorylate additional proteins and thus a cascade of protein interactions is established.
- Ultimately activates a transcription factor. This transcription factor then activates or inhibits gene expression.
Is mediated through signal transduction pathways as well but does not involve diffusable factors
Juxtacrine signalling
Three ways juxtacrine signalling occurs
- A protein on one cell surface interacts with a receptor on an adjacent cell in a process analogous to paracrine signalling. Example. Notch pathway.
- Ligands in the extracellular matrix secreted by one cell interact with their receptors on neighboring cells.
- Theres direct transmission of signals from one cell to another by gap junctions.
Receptors that link extracellular molecules such as fibronectin and laminin to cells are called
Integrins
Give examples as to why there is a great amount of redundancy built into the process of signal transduction
Paracrine signalling molecules often have many family members such that other genes in the family may compensate for the loss of one of their counterparts. Thus the loss of a function of a signaling protein through a gene mutation OES it necessarily result in abnormal development or death.
Four group of GDFs (growth and differentiation factors)
- Fibroblast growth factor
- WNT
- Hedgehog
- Transforming growth factor beta ( TGF-B)
Each family of GDFs interacts with its own family of receptors, and these receptors are as important as the signal molecules themselves in determining the outcome of a signal.
How many FGF genes have been identified?
Approximately two dozen and they can produce hundreds of protein isoforms by altering their RNA splicing or their initiation codons
FGF proteins produced by these genes activate a collection of tyrosine receptor kinases called
Fibroblast growth factor receptors (FGFRs)
FGFs are important for
- Angiogenesis
- Axon growth
- Mesoderm differentiation
FGF 8 is?
Important for development of the limbs and parts of the brain
Why was the gene named hedgehog
Because it coded for a pattern of bristles on the leg of Drosophila that resembled a shape of the hedgehog
Enumerate the 3 hedgehog genes in mammals
- Desert
- Indian
- Sonic hedgehig.
How many WNT genes are related to the segment polarity gene, wingless in Drosophila?
At least 15
WNT receptors are members of what family?
Frizzled family of proteins
WNT proteins are involved in
- Regulating limb patterning
- Midbrain development
- Some aspects of somite and urogenital differentiation among other actions.
The TGF beta superfamily has more than 30 members enumerate at least 4
- The TGF-Bs
- The bone morphogenetic proteins (BMPs)
- The activin
- The müllerian inhibiting factor (MIF, anti-mullerian hormone)
TGF-B members are important for
- Extracellular matrix formation
2. Epithelial branching that occurs in lung, kidney, and salivary gland development.
The BMP family includes
Bone formation and us involved in regulating cell division, cell death (apoptosis), and cell migration among other functions
Another group of paracrine signaling molecules important during development are neurotransmitters including
- Serotonin
- Y-amino butyric acid (GABA)
- Epinephrine
- Norepinephrine
That act as ligands and bind to receptors just as proteins do. They also provide important signals for embryological development.
Serotonin (5-HT) acts as a ligand for a large number of receptors most of which are G protein coupled receptors through this it
Regulates a variety of cellular functions, including cell proliferation and migration, and us important for establishing laterality, gastrulation, heart development, and other processes during early stages of differentiation.
Norepinephrine acts through receptors and
Appears to play a role in apoptosis (programmed cell death) in the interdigital spaces and in other cell types
A secreted molecule that would establish concentration gradients and instruct cells in how to become different tissues and organs
Morphogen
Closes protein to being the master morphogen
Sonic hedgehog
Sonic hedgehog is a protein involved in
- Development of the vasculature
- Left-right axis formation
- Midline
- Cerebellum
- Neural patterning
- Limbs
- Smooth muscle patterning
- Heart
- Gut
- Pharynx
- Lungs
- Pancreas
- Kidneys
- Bladder
- Hair follicles
- Teeth
- Thymocytes
- Inner ear
- Eyes
- Taste buds
The SHH protein has some unique characteristics
- After translation it is cleaved and cholesterol is added to the C-terminus of its N-terminal domain.
- It is the addition of cholesterol that links SHH to the plasma membrane.
- Then, a palmitic acid moiety is added to the N terminus and SHH becomes fully functional.
- Its release from the plasma membranes is produced by the transmembrane protein Dispatched
- At this point SHH can establish the concentration gradients characteristic of its action as a morphogen
The process whereby a tissue becomes longer and narrower
Convergent extension
The pathway that regulates convergent extension
The planar cell polarity (PCP) pathway
Give examples of convergent extension
- During neural tube formation (neurulation), the neural plat narrows and elongated to form the neural groove between the neural folds.
- During gastrulation cells move medially and the embryonic axis elongates.
- Elongation of the cardiac outflow tract .
- Movement of the lateral body wall toward the midline.
Notch receptor proteins binds to
- Delta protein
- Serrate protein
- LAG-2 /jagged protein
receptors that link extracellular molecules such as fibronectin and laminin
Integrins
What forms scaffolds for cell migration?
Fibronectin molecules
The milieu consists of large molecules secreted by cells including:
- collagen
- proteoglycans (chondroitin sulfate and hyaluronic acid)
- glycoproteins (e.g fibronectin and laminin)
