Final extra material Flashcards
Wnt (Wnt/beta-catenin) signaling pathway
fig 3.16
What are antagonists of paracrine factors?
secreted molecules that block the action of paracrine factors
What is involved in the downregulation of BMP?
- Noggin
- Chordin
What is Direct Cell Contact?
Contact between the inducing and responding cells
What does the delta-notch pathway do?
controls multiple cell differentiation processes during embryonic and adult life and is dysregulated in many cancers
Where do you see the delta noch pathway?
- Gliogenesis
- Left-reight asymmetry determination
- Somite Formation
What is the function of Lunatic Fringe?
- Acts in the Golgi to modify Notch and alter the ability of Notch to bind its ligand Delta
- Establishes the anterior boundary of somites
How is the extracellular matrix involved in cell communication?
The matrix of one cell induces change in another cell
What are Integrin?
- The principal receptors used by animal cells to bind to the extracellular matrix
- Heterodimers
- Function as transmembrane linkers between the extracellular matrix and the actin cytoskeleton
What are some signaling pathway examples?
- Branch points for multiple responses
- Crosstalk; integration of multiple signals
- Reciprocal communication/induction
How do cells become committed to forming a particular tissue?
Cells receive signals that cause them to develop down a certain pathway
Cell Fate is…
What a cell or tissue will develop into during the development
When a cell first becomes committed to a particular fate, it does not appear phenotypically different from its uncommitted state.
Having a particular normal fate does not imply that a cell could not develop differently if placed in a different environment
Potency is…
What a cell or tissue could become during development if it were allowed to develop in another envirinent
What is cell commitment?
The state in which a cell’s developmental fate has become restricted even though it is not yet displaying overt changes in cellular biochemistry and function
Cell Specification…
Occurs when a group of cells gain a bias toward certain fate (the normal fate) and if isolated and cultures in a neutral medium they develop according to normal cell fate
Determination is when…
Cell fate becomes irreversible: a stable change in the internal state of a cell occurs such that its fate is now fixed, or determined.
A determined cell can not longer develop in accordance with new environment signals
What is induction?
Instructive signals from one cell or tissue that cause a change in the cellular behavior of adjacent responding cells
What is competence?
Cells in the presence of the signal must be competent to respond for a change to occur
What are two ways cells can be differentially induced?
- Morphogen Gradients
- Lateral Inhibition
Morphogen Gradients
Cells respond to signals in a concentration-dependent manner
What are morphogens used for?
To give positional information
What are morphogens?
signaling molecules that emanate from a restricted region of tissue and spread away from their source to form a concentration gradient.
What are morphogen gradients used for?
they are used for spatial regulation of gene expression
Morphogen-concentration-dependent induction of….
gene expression
activators and repressors determine
expression patterns
When does combinatorial gene control occur?
when gene expression requires the presence or absence of a particular combination of regulatory proteins (TFs)
TFs can be used in different combinations to do what?
to regulate different genes
enabling the organism to have innumerable expression patterns with a limited number of TFs
what is a regulatory gene hierarchy?
it is a cascade of gene expression where the gene products in each class control the expression of the genes in the next class
Pax
regional specifications
How does the cascade of gene expression begin?
It begins when signals from the maternal proteins activate a set of genes called “gap” genes along with the axis between the anterior and posterior halves of the embryo
Hox
Segmental specifications
How are “gap genes” expressed?
each gap gene is expressed in a specific domain in the embryo
What are pair-rule genes?
they refine domains
Lateral inhibition
One cell produces an inhibitor that prevents neighboring cells from differentiation with a particular fate.
What are the steps of lateral inhibition
- Cell starts off as equivalent
- A stochastic (chance) event causes one cell to produce more of a signal molecule at some particular critical time
- This difference is amplified until the cells become different types
How do the cells of the early embryo appear?
they are morphologically identical
they are only distinguished only by their inner/outer positions at 16-and 32- cell stages
Totipotency exists until…
at least 16-cell stage
Inner Cells —>
inner cell mass
Outer Cells —>
trophoblast
Trophoblast
supporting structures;
contributes to placenta
Cells of the Inner Cell Mass are…
pluripotent
Cultured ICM cells =
ES cells ( embryonic stem cells )
What do polar cells with apical and basal surfaces form?
outer cells
What do nonpolar cells form?
inner cells
What is the role of Oct 4?
Oct4 plays an essential role in the development of pluripotent cells in the embryo and plays a role in the self-renewal of its in vitro counterpart, (ES) cells
Oct4 is an essential…
Transcriptional regulator
What are Oct4’s functions during different stages
- Pluripotency maintenance
- Cell differentiation
- Transdifferentiation
- Reprogramming to iPS cells
How does the differentiation into trophoblasts & ICM occur?
This occurs by the reciprocal interaction between Oct4 & Cdx2
The pluripotency network is maintained by what 3 transcription factors?
- Oct4
- Nanog
- Sox2
What does ICM differentiate into?
Epiblast and Hypoblast
What orchestrates the differentiation to epiblast and hypoblast in the late blastocyst or (bilaminar disk)?
Nanog and Gata6
What is asymmetry?
Allows for differential cell fates and body axis formation
When is asymmetry established?
it is established during egg formation and/or very early development
What is localized asymmetrically in the frog egg?
Determinants
What are some antagonists of BMP?
- Noggin
- Chordin
- DAN/cerberus
What are some antagonists of Wnt?
- Dickkopf
- Cerberus
Nodal
Lefty-1
Cerberus-like
What are the steps in producing the anterior and posterior axis?
- Formation of bilaminar embryo & posterior marginal zone
- Two signaling centers develop.
The Wnts form what?
The posterior marginal zone
What does the nodal do?
It promotes primitive streak formation in the epiblast
What are the anterior signaling centers?
Anti-Wnt
nodal antagonists
What are the posterior signaling centers?
Wnts
Nodal (TGF-beta)
Examples of Left-Right Asymmetry
- Visceral organs of the thorax
- Brain and Nervous system
- Immune hypersensitivity
What are the three principle steps of left-right asymmetry?
- Breaking bilateral symmetry
- Propagation & reinforcement of an asymmetric signal
- Translation of the signals into asymmetric organ morphogenesis
What is formed at the end of gastrulation/early embryogenesis
- Trilaminar embryo
- 2 signaling centers
- Notochord (source of inducing signals)
- Tissue specification that are not obvious
What happens during weeks 4-8: organogenesis?
- Major external & internal structures are established
- By the end of the 8th week (10 weeks gestational age), the shape of the embryo has a distinctly human appearance.
What are some major large-scale changes that happen in Organogenesis?
- Organs and tissues form from the germ layers
- Cardiovascular system becomes functional
- Exposure to teratogens may cause major congenital abnormalities
- Mesodermal and endodermal organs occur synchronously with neural tube formation in an anterior and posterior direction
- The embryo folds into the “tube-within-a-tube” body plan as development proceeds into organogenesis (bird and mammal)
- Pattern formation: the embryo is organized into large regions, then smaller regions, and finally segments from which tissues and organs are produced
The formation of mesodermal and endodermal organs occurs synchronously with…
neural tube formation in an anterior to posterior direction
What are the three flat germ layers
- Lateral folds
- Head Fold
- Tail Fold
Folding results from…
rapid growth of the embryo
What is the formation of the body axes known as?
Breaking symmetry
What are steps in pattern formation?
- Formation of the body axes
- Organization of the embryo into smaller regions – segments
- Segments develop specific characteristics
- Tissues & organs are produced
What are the steps in pattern formation?
- Formation of the body axes
- Organization of the embryo into smaller regions – segments
- Segments develop specific characteristics
- Tissues & organs are produced
What forms from the surface ectoderm?
- Epidermis
- Lens, cornea
- Anterior pituitary
What forms from the neural crest?
- Facial Cartilage
- Peripheral nervous system
What forms from the neural tube?
- Brain
- Neural Pituitary
- Spinal cord
- Retina
What two processes help form the neural tube?
Cell shape and adhesion changes
What two processes help form the neural tube?
Cell shape and adhesion changes
What are the derivatives of the Rhombencephalon?
Metencephalon and Myelencehalon
What are the derivatives of the Prosencephalon?
Telencephalon and Diencephalon
What 5-part brain structure forms the cerebrum?
Telencephalon
What 5-part brain structure forms the Optic Vesicle?
Diencephalon
What 5-part brain structure forms the Midbrain
Mesencephalon
What 5-part brain structure forms the cerebellum?
Metencephalon
What 5-part brain structure forms the Medulla?
Myelencephalon
What does BMP-4 allow?
Ventral development
When chordin and noggin are present what is allowed to develop?
Dorsal development is allowed
What axis does Nodal and Wnts gradients form?
Anterior-Posterior
What signaling centers develop the Anterior region?
Anti-wnts
Nodal antagonists
What two transcription factors are expressed on either side of the isthmic organizer?
Otx-2 (Anterior side, Forebrain/Midbrain)
Gbx-2 (Posterior side, Hindbrain/spinal cord)
Where are FGF-8 and Wnt-1 each synthesized in relation to the isthmic organizer?
FGF-8: Posterior
Want-1: Anterior
FGF-8 and Wnt-1 induce a gradient of which transcription factors on both sides of the isthmic organizer?
Engrailed (En-1 and En-2) and Pax2 and Pax5
Which transcriptions factors subdivide the early neural tube into three divisions?
Pax2/5 and Pax 6
In posterior neural development, what three signaling pathways are involved?
Wnt
FGF
Retinoic acid
What does wnt/B-catenin activity to do the embryonic nervous system?
It caudalizes the embryonic nervous system
How are Hox genes expressed?
In a temporal and spatial order that reflects their order on the chromosome
What are Hox genes regulated by?
Transcription factors
Gene position
miRNAs
In the formation and differentiation of mesoderm, how do dorsal/ventral divisions form?
As medial/lateral divisions respectively.
Medial becomes dorsal, lateral becomes ventral
What are the four trunk subdivisions of mesoderm?
Intermediate mesoderm
Chordamesoderm
Paraxial mesoderm
Lateral plate mesoderm
What does the chordamesoderm form?
Notocord
What does the paraxial mesoderm form?
Somites, which forms:
Sclerotome
Dermatome
Myotome
What does the sclerotome form?
Axial skeleton
What does the dermatome form?
Dermis of the back
What does the myotome form?
Epaxial myotome —> back muscles
Hypaxial myotome —> limb muscles
What does the intermediate mesoderm form?
The urogenital system:
Kidneys and Gonads
What mesoderm layers does the lateral plate mesoderm split into?
Somatic mesoderm
Splanchnic mesoderm
What does the somatic mesoderm form?
Limb skeleton
Blood vessels
What does the splanchnic mesoderm form?
Smooth muscle of the gut and respiratory tract
Heart
Circulatory system
