Unit 7 - Mechanisms of Development Flashcards
what does the environment have to do with genes?
sets of genes act differently in different environments (gene-environment interactions)
-depends on cell-cell communication
how many human genes are similar to flies and worms?
40% (humans and nematodes have ~20,000 genes, fruit flies have 14,000 genes)
how many genes are similar to mice?
92%
what are homologous genes?
genes similar in structure, evolutionary origin, and function to a gene in another species
what is the significance of Engrailed-1 gene in mice VS fruit flies?
Engrailed-1 codes for cerebellum development in mice
- if it is removed, the cerebellum will not develop
- if Engrialed-1 from fruit fly is inserted, the cerebellum will develop again
what is the concept of genome equivalence?
genetic material is identical in every cell, but different cells express different sets of genes
what is differential gene expression?
only a small percentage of genome is expressed in cell types
at what levels is gene expression regulated?
- differential gene transcription
- selective nuclear RNA processing
- selective mRNA translation
- differential protein modification
what are 4 essential cellular processes by which an embryo is constructed?
- cell proliferation - produce many cells from one
- cell specialization - creates cells with different characteristics at different positions
- cell interactions - coordinating behavior of one cell with that of its neighbors
- cell movement - rearranging cells to form structured tissues and organs
what is induction?
one group of cells changes behavior of an adjacent set of cells
- inducers (tissue that provide signal that changes behavior of target signal)
- responders (tissues that must have competence to respond to signal)
how is competence acquired and examples with PAX6?
actively acquired
-PAX6 makes ectoderm competent to respond to inductive signals from optic vesicle, so only cells expressing PAX6 can become eye cells
what do mutations in PAX6 cause?
aniridia (affects iris, intraocular pressure, lens, cornea, and optic nerve)
- underlying mech unknown, but due to failure in optic vesicle rim development between weeks 12-14 of gestation
- homozygous loss of PAX6 causes fatal condition where eye is not formed at all
what are 2 types of signaling methods between inducers and responders?
- Juxtacrine signaling - direct contact between inducing and responding cells
- Paracrine signaling - diffusion of inducers from one cell to another
what are morphogens?
paracrine signaling molecules that cause concentration-dependent effects
-acts in concentration-dependent manner (lower concentration gradient at ends means response either isn’t that high, or it induces something completely different)
relationship between SHH, PTCH, and SMO
SHH secreted ligand binds to PTCH transmembrane protein, which inhibits SMO, so that GLI factors can turn on gene expression
what are the major ligands for the roofplate and floor plate?
roof: BMP and WNT
floor: SHH
situs solitus VS situs inversus VS heterotaxy (also situs ambiguus)
SS: normal orientation
SI: complete mirror-reversal of organ left-right asymmetry (low risk of malformations b/c concordant alignment)
H: some of organs are SS, others are SI
what things are heterotaxy related to?
1: 10,000 live births
- congenital heart defects
- asplenia (if right isomerism) or polysplenia (if left isomerism)
- malrotation of intestine (causes volvulus twisted bowel that causes obstruction)
what is the key to the basis of left-right asymmetry?
asymmetric gene expression that precedes first gross anatomical asymmetries
-Nodal codes for member of TGFb superfamily; signal is relayed on only the left side
Kartagener’s triad
- bronchiectasis
- male infertility
- situs inversus (~50%)
these symptoms were due to deficient cilia and flagella, such that ciliary beating somehow controls which way the left-right axis is oriented
how is the Nodal signaling cascade involved in left-right patterning?
cell-cell signaling cascade controls relay of Nodal asymmetry that depends on feedback loops involving Nodal together with Lefty genes (Nodal antagonists)
-Pitx2 links outcome of Nodal/Lefty interactions to anatomical development
Nodal-Pitx2 signaling
transfer of molecular left-right asymmetry to organs
-Pitx2 is expressed on left side of developing heart, gut, and brain
what is the general cause of asymmetry?
morphogen gradient is asymmetric, from right to left
- LR signal (Ca++) causes differential gene expression and cell-cell signaling cascade (LPM –> Nodal –> Lefty –>Pitx2)
- this causes the rotation for asymmetry
