Unit 7 - Mechanisms of Development

Question 1

what does the environment have to do with genes?

Answer 1

sets of genes act differently in different environments (gene-environment interactions)
-depends on cell-cell communication

Question 2

how many human genes are similar to flies and worms?

Answer 2

40% (humans and nematodes have ~20,000 genes, fruit flies have 14,000 genes)

Question 3

how many genes are similar to mice?

Answer 3

92%

Question 4

what are homologous genes?

Answer 4

genes similar in structure, evolutionary origin, and function to a gene in another species

Question 5

what is the significance of Engrailed-1 gene in mice VS fruit flies?

Answer 5

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

Question 6

what is the concept of genome equivalence?

Answer 6

genetic material is identical in every cell, but different cells express different sets of genes

Question 7

what is differential gene expression?

Answer 7

only a small percentage of genome is expressed in cell types

Question 8

at what levels is gene expression regulated?

Answer 8

1. differential gene transcription
2. selective nuclear RNA processing
3. selective mRNA translation
4. differential protein modification

Question 9

what are 4 essential cellular processes by which an embryo is constructed?

Answer 9

1. cell proliferation - produce many cells from one
2. cell specialization - creates cells with different characteristics at different positions
3. cell interactions - coordinating behavior of one cell with that of its neighbors
4. cell movement - rearranging cells to form structured tissues and organs

Question 10

what is induction?

Answer 10

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)

Question 11

how is competence acquired and examples with PAX6?

Answer 11

actively acquired
-PAX6 makes ectoderm competent to respond to inductive signals from optic vesicle, so only cells expressing PAX6 can become eye cells

Question 12

what do mutations in PAX6 cause?

Answer 12

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

Question 13

what are 2 types of signaling methods between inducers and responders?

Answer 13

1. Juxtacrine signaling - direct contact between inducing and responding cells
2. Paracrine signaling - diffusion of inducers from one cell to another

Question 14

what are morphogens?

Answer 14

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)

Question 15

relationship between SHH, PTCH, and SMO

Answer 15

SHH secreted ligand binds to PTCH transmembrane protein, which inhibits SMO, so that GLI factors can turn on gene expression

Question 16

what are the major ligands for the roofplate and floor plate?

Answer 16

roof: BMP and WNT
floor: SHH

Question 17

situs solitus VS situs inversus VS heterotaxy (also situs ambiguus)

Answer 17

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

Question 18

what things are heterotaxy related to?

Answer 18

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)

Question 19

what is the key to the basis of left-right asymmetry?

Answer 19

asymmetric gene expression that precedes first gross anatomical asymmetries
-Nodal codes for member of TGFb superfamily; signal is relayed on only the left side

Question 20

Kartagener’s triad

Answer 20

• 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

Question 21

how is the Nodal signaling cascade involved in left-right patterning?

Answer 21

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

Question 22

Nodal-Pitx2 signaling

Answer 22

transfer of molecular left-right asymmetry to organs

-Pitx2 is expressed on left side of developing heart, gut, and brain

Question 23

what is the general cause of asymmetry?

Answer 23

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