2-36 Mechanisms of Development

Question 1

what allows us to use animal models?

Answer 1

genetic similarities. 40% of human genes are found in flies and roundworms

Question 2

what are homologlous genes?

Answer 2

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.)

Question 3

what is the idea of genome equivalence?

Answer 3

The idea that every cell in the body contains the same genome. Proven by cloning “dolly” the sheep with a single skin cell.

Question 4

Differential Gene Expression

Answer 4

The idea that different cell types express different genes.

Question 5

induction

Answer 5

– 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.

Question 6

optic lens example

Answer 6

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

Question 7

aniridia

Answer 7

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

Question 8

morphogens

Answer 8

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

Question 9

signaling cascades

Answer 9

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

Question 10

describe the TGFb signaling pathway

Answer 10

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

Question 11

the internal organs are placed asymmetrically within the trunk of the body. what is the key to this?

Answer 11

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

Question 12

describe nodal and what it does

Answer 12

nodal is a secreted molecule that turns on transcription of itself and downstream TF PitX2 and antagonist lefty.

Question 13

lefty

Answer 13

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

Question 14

pitx2

Answer 14

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

Question 15

incorrect localization of gene expression leads to

Answer 15

changes in body asymmetry, as opposed to normal situs solitus.

inverted layout - situs inverses - no clinical issues
and
situs ambiguous - irregular layer

Question 16

calcium is a morphogen, TF

Answer 16

calcium is not a morphogen. it is a downstream effector

Question 17

describe role of cilia

Answer 17

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

Question 18

how can drugs alter developing symmetry?

Answer 18

if they elevate or reduce calcium levels

Question 19

Kartagener’s Triad

Answer 19

due to immotile cilia

bronchiectasis - cilia unable to move mucus out
infertility - sperm flagella non-motile
situs inversus (50%)

Question 20

cardiac looping to the right is…

Answer 20

highly conserved and important in vertebrates

Question 21

sonic hedgehog protein does what?

Answer 21

binds receptor, inhibits activity of another receptor, represses gene expression

Question 22

describe competence molecules

Answer 22

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

Question 23

genes in the embryo can be

Answer 23

differentially regulated and timing is important

regulated by

• differential gene expression
• selective nuclear RNA processing
• selective mRNA translation
• differential protein modification

Question 24

if all the genes in all cells are the same, how do we get differentiation?

Answer 24

through differential expression.

only a small percentage of the genome is expressed in each cell type