Body Axes and Neurulation

Question 1

Cell migration and specification (gastrulation) are controlled by what?

Answer 1

FGF8 (made by primitive streak cells)….establishes expression of Nodal on LEFT side only (before gastrulation it’s symmetric)

Question 2

Primary germ layers

Answer 2

Top to bottom:

Ectoderm
Mesoderm
Endoderm

Question 3

What expresses genes for head formation and TF’s “cerebrus” and “lefty”?

Answer 3

AVE (anterior visceral endoderm)

Question 4

Gene for movement of cells from primitive streak

Answer 4

Brachyury (T) gene

Question 5

Gene for primitive streak formation

Answer 5

Nodal gene

Question 6

Gene for body axis formation

Answer 6

Goosecoid gene

Question 7

Gene for the formation of notochord

Answer 7

HNF-3β

Question 8

Gene for head formation

Answer 8

Lim-1

Question 9

Goosecoid gene overexpression

Answer 9

2 heads

Question 10

What does T gene (brachyury) antagonize?

Answer 10

BMP-4

Absense of T (brachyury) gene → no lower body/very small

Question 11

Activin gene inhibits what and is expressed on which side?

Answer 11

Inhibits Shh (sonic hedgehog) expression

Activin expressed on RIGHT, so it blocks Shh on the right

Question 12

FGF8 induces expression of what?

Answer 12

Lefty2 (Lefty 1 expressed in forming neural tube)

5HT dependent on serotonin

5HT→FGF8→Nodal and Lefty2→PITX2

Question 13

PITX2 does what?

Answer 13

TF responsible for establishing LEFT sidedness (defects can cause organs to be on opposite sides)

Question 14

5HT is important in what?

Answer 14

Establishing laterality

Disruptions can result in situs inversus, dextrocardia and heart defects

↑ congenital heart defects in children born to mom’s who take antidepressants from selective serotonin reuptake inhibitors (SSRI’s)

Question 15

Gene for Right-sided development

Answer 15

Snail

repressed by Nodal

Question 16

What blocks BMP-4?

Answer 16

Noggin
Chordin
WNT3a
FGF

If BMP4 is present: Ectoderm → Epidermis
If BMP4 is BLOCKED: Ectoderm → neural plate

Question 17

Epidermis has a lot of what?

Answer 17

BMP4

It’s going to induce a new signaling center in roof plate

Question 18

What transcription factor induces a floor plate in the ventral floor of neural tube?

Answer 18

Shh (Sonic hedgehog)

Question 19

What is Rachischisis?

Answer 19

Neural tube defect

Neural tube fails to close during week 4 of development

Most severe form of spina bifida. Causes paralysis from the level of the defect and caudally

Question 20

What is neurulation?

Answer 20

Refers to the formation and closure of neural tube

Question 21

What is Anencephaly?

Answer 21

Cranial Neuropore fails to close (on the head)

Question 22

What is Encephalocele?

Answer 22

Failure of back of head to close (occipital region)

Anterior (frontal) Encephalocele: failure on front of face to close

Question 23

Spina bifida with meningomyelocele

Answer 23

Large skin-covered bulge at posterior lower lumbar spine. There is also paralysis of the baby’s legs

Question 24

What causes lifelong paralysis from Spina Bifida?

Answer 24

If it isn’t fixed before 38 weeks

Question 25

How does folic acid prevent neural tube defects?

Answer 25

Daily intake of 0.4mg of folic acid (folate) will decrease the odds of it Prevents 70% of human neural tube defects (NTD's) but mode of action is unclear

Question 26

An increase of what appears to prevent the closing of the neural tube?

Answer 26

Increased homocysteine levels - Tested by alpha-fetoprotein (AFP) - AFP is made in liver. With NTD, AFP leaks into amniotic fluid across the placenta. Maternal blood can be tested for OPEN tube defects only

Question 27

What does BMP do?

Answer 27

Induces the neural crest Abnormal concentrations of BMP/FGF's → neural crest defects BMP, FGF, WNT proteins → induce PAX3 to "specify" the neural plate border SNAIL and FOXD→specify cells as neural crest SLUG → promotes crest cell migration from neuroectoderm

Question 28

Ectodermal dysplasia (ED)

Answer 28

Affects the ectoderm (outer layer of tissue in developing baby) When child has 2 types of abnormal ectodermal features- malformed teeth, sparse hair etc

Question 29

What does the Lateral Mesoderm differentiate into?

Answer 29

Appendicular skeleton, dermis of skin

Question 30

Pigmentary Disorders: Vitiligo

Answer 30

Loss of melanocytes | spotchy