Genetics Of Early Dev't. & Molecular Genetics

Question 1

Describe Nodal.

Answer 1

A type of TGF-Beta “transformational growth factor” protein expressed on the node (site of invagination) and along the primitive streak. Induces AVE which inhibits Nodal for anterior dev’t.

Question 2

Describe BMP4.

Action, antagonists, expression

Answer 2

“Bone morphogenetic protein” functions to inhibit initial mesoderm and ectoderm development.
Antagonists: noggin, chordin and lefty
Expression:
-HIGH -> epidermis (skin)

Question 3

Why is AVE important in early development?

Answer 3

Anterior visceral endoderm produces TFs that pattern the head in the early embryo.
It is made by and inhibits Nodal expression for time to work on anterior (head) dev’t.

Question 4

What is the Hatched Area and what is Goosecoid?

Answer 4

The Hatched area is known for broad expression of BMP-4.
Goosecoid is a TF found in the node that allows for induction of anterior structures, by the mesoderm moving towards the head.

Question 5

Describe FGF8.

Function, where expressed, regulation

Answer 5

Functions in somite formation that leads to left-right symmetry of the embryo via signaling cascade. It’s presented to receptors by heparan sulfate.
Promotes chordin/noggin to inhibit BMP4, so mesoderm and neural tissue (from ectoderm) can develop.
Regulated by RA (retinoic acid) in controlled amounts.

Question 6

What diseases result from too much…
Goosecoid?
Retinoic Acid?

Answer 6

1. Xenopus - double-headedness; altered anterior mesoderm
2. Sirenomelia - lower limb abnormality; posterior mesoderm deficiency
   * Too much RA early shuts off FGF8 prematurely leading to deficit*
   * OR too little chordin, noggin, Brachyury*

Question 7

Describe Retinoic Acid

Answer 7

An endogenous steroid expressed more anteriorly to FGF8 in (rostral to caudal) mesoderm formation. It binds to nuclear receptors.
Can be a TERATOGEN

Question 8

How is FGF related to Hox genes?

Answer 8

FGF exposure is related to 5’ Hox gene expression in the Posterior mesoderm.

Question 9

Describe the steps leading to posterior mesoderm deficiency starting with RA.

Answer 9

Too much RA (teratogen) -> 
Too little FGF (premature shutdown) ->
Too little 5' Hox gene expression ->
No Posterior Mesoderm ->
Sirenomelia

Question 10

Describe Hox genes.

Answer 10

They express specific embryonic domains that function in that part of the body and are ordered from 3’ (HEAD) to 5’ (TAIL). They correlate strongly to the order of certain structures

Question 11

A homeotic mutation occurs where one structure is _______ or _______. The homeobox DNA sequence is an area of observed genes with _ _ _ _ rich region. A homeodomain encodes homeobox proteins that have 3 _____ _______ with amino acids in helix #3 coming into contact with DNA.

Answer 11

Replaced or Duplicated;
TAAT rich region;
Alpha helices

Question 12

Hox genes are highly ________ across species.

Describe orthologs and paralogs.

Answer 12

CONSERVED
Orthologs - expressed BETWEEN species
Paralogs - homologous genes WITHIN species

Question 13

In Mouse Hox genes:
Gain of function mutations lead to _______ transformations.
Loss of function mutations lead to _______ transformations.

Answer 13

Posterior;

Anterior

Question 14

What is Brachyury? What does it lead to when defected?

Answer 14

T-box Transcription Factor Gene;

When defective: leads to deficient posterior mesoderm.

Question 15

Describe the RAldh2.

Answer 15

This is a gene controlled by RA and nuclear receptors, present in somites (condensed mesoderm).

Question 16

Describe TGF-Beta.

Answer 16

It functions through tyrosine/serine kinase signaling and is involved with the formation of mesoderm from migrating neural crest cells.