Flashcards in 2-36 Mechanisms of Development Deck (24)
what allows us to use animal models?
genetic similarities. 40% of human genes are found in flies and roundworms
what are homologlous genes?
Genes found in different species that are similar in structure, in evolutionary origin, and likely in function as well. (e.g. A mouse that artificially produces a homologous fruit fly brain developmental protein still has successful brain development.)
what is the idea of genome equivalence?
The idea that every cell in the body contains the same genome. Proven by cloning "dolly" the sheep with a single skin cell.
Differential Gene Expression
The idea that different cell types express different genes.
– The act by which one group of cells (inducers) changes the behavior of an adjacent group of cells (responders). It is carried out by chemical messengers, either through cell-cell contact (short-range) or by sending the messenger through the ECM (long-range). Only competent cells will be able to respond to and/or receive those signals. Competence of cells is actively acquired.
optic lens example
offshoot of neural tube called optic vesicle induces ectoderm cells to form lens when in contact with the ectoderm.
if optic vesicle removed OR added to other part of frog, the ectoderm will not form a lense
proper inducer and proper responders (in this case with expression of PAX-6 TF in the cell)
expression of Pax6 grants competence to the responders
when an individual lacks a copy of the Pax6 gene
-several eye structures including the iris and optic nerve are affected
lacking both copies leads to a fatal condition
paracrine signaling molecule that cause concentration-dependend events.
can generate more than one cell type by establishing a gradient in conencretation (different concentrations throughout the gradient will direct cells into different developmental pathways
occur via juxtacrine (cell-cell direct) or paracrine
when signal received - cascade directed by intracellular proteins leads to altered metabolism, altered gene expression, and altered cell shape/movement
describe the TGFb signaling pathway
begins with cell surface receptor recognition of a TGFB family molecule (TGFb, BMP, and Nodal)
2. SMAD transcription factors are phosphorylated - move to nucleus and modulate gene expression
the internal organs are placed asymmetrically within the trunk of the body. what is the key to this?
asymmetric gene expression which is facilitated by ciliary beating by ciliated cells which creates an uneven distribution of Ca+2 favoring the left side
the signal is then relayed to create a broad stripe of nodal expression in the lateral plate mesoderm solely along the left side of the embryo body, leading to differential gene expression
describe nodal and what it does
nodal is a secreted molecule that turns on transcription of itself and downstream TF PitX2 and antagonist lefty.
upregulated by nodal - lefty functions to restrict the asymmetric domain of nodal signaling by keeping gene expression exclusively on the left side of the embryo
upregulated by nodal - expressed on left side of developing heart, gut, and brain. thought to regulate expression of genes that mediate asymmetric morphogenesis of these organs
incorrect localization of gene expression leads to
changes in body asymmetry, as opposed to normal situs solitus.
inverted layout - situs inverses - no clinical issues
situs ambiguous - irregular layer
calcium is a morphogen, TF
calcium is not a morphogen. it is a downstream effector
describe role of cilia
creates asymmetric flow which generates areas with higher signaling calcium on the left, causes nodal signaling that turns on other genes. these genes are important for forming asymmetries as heart and gut begin to develop
how can drugs alter developing symmetry?
if they elevate or reduce calcium levels
due to immotile cilia
bronchiectasis - cilia unable to move mucus out
infertility - sperm flagella non-motile
situs inversus (50%)
cardiac looping to the right is...
highly conserved and important in vertebrates
sonic hedgehog protein does what?
binds receptor, inhibits activity of another receptor, represses gene expression
describe competence molecules
on a molecular level, all of the docking proteins, signaling molecules, and effector proteins that lead to altered metabolism, altered gene expression, or altered cell shape/movement
genes in the embryo can be
differentially regulated and timing is important
-differential gene expression
-selective nuclear RNA processing
-selective mRNA translation
-differential protein modification