Van Raamsdonk Lectures

Question 1

When does primary neurulation occur in humans?

Answer 1

Day 18-23

Question 2

When does secondary neurulation occur in humans?

Answer 2

Day 28-48

Question 3

What closure point(s) is/are affected in exencephaly/anencephaly?

Answer 3

Closure points 2 and 3

Question 4

The lack of which transcription factor is responsible for exencephaly/anencephaly?

Answer 4

Grhl3

Question 5

What closure point(s) is/are affected in craniorachischisis?

Answer 5

Closure point 1

Question 6

The lack of which transcription factor leads to cranioarchischisis?

Answer 6

Celsr1

Question 7

Deficiency in which vitamin is linked to NTDs?

Answer 7

Vitamin B9 (folate)

Question 8

What are the 6 criteria for determining whether something is a teratogen?

Answer 8

1. Abrupt increase in frequency of a defect or syndrome 2. Increase of syndrome associated with agent 3. Agent was present during critical stage 4. Agent produces birth defects in animal models 5. Agent can cross placenta (exceptions) 6. Mechanism of teratogenesis makes biological sense

Question 9

What were 4 reforms made to drug regulation following the thalidomide disaster?

Answer 9

Federal regulation of clinical trials, informed consent prior to enrolment in clinical trial, pre-clinical trials must include more than one animal model, companies must do more to show that drugs are safe before approval

Question 10

What is the thalidomide sensitive window?

Answer 10

4th week of pregnancy

Question 11

Which cells spread Zika virus around the fetus?

Answer 11

Hoffbauer cells

Question 12

What is the critical period of Zika virus?

Answer 12

12-16 weeks

Question 13

What is the proposed mechanism for thalidomide syndrome?

Answer 13

Thalidomide causes CRBN to target p63 as a neosubstrate; CRBN is an E3 ubiquitin ligand, so it targets p63 for degradation; p63 levels maintain high FGF in AER, which is necessary for limb development; without high FGF, phocomelia occurs

Question 14

What is the proposed mechanism for Zika virus causing microcephaly?

Answer 14

ZIKV unregulates TP53 protein, which causes apoptosis through S-phase arrest

Question 15

What are the pluripotent factors expressed by neural crest cells?

Answer 15

Nanog, Oct4, and Klf4

Question 16

What signalling molecules induce neural crest cells?

Answer 16

Intermediate FGF, intermediate Wnt, intermediate BMP

Question 17

Which tissue is made where BMP signalling is high?

Answer 17

Skin

Question 18

Which signalling molecules induce EMT in neural crest cells?

Answer 18

BMP and Wnt cascade

Question 19

What are the two key TFs for EMT in cranial neural crest cells?

Answer 19

Snail and Foxd3

Question 20

Which are the negative regulators of neural crest cell migration?

Answer 20

Ephrins (bind ephrin receptors of neural crest cells) and neurophilins (bind semaphorin on neural crest cells)

Question 21

Which stream of neural crest cells makes PA1?

Answer 21

Stream 1

Question 22

Which stream of neural crest cells makes PA2?

Answer 22

Stream 2

Question 23

Which stream of neural crest cells makes PA3 and PA4?

Answer 23

Stream 3

Question 24

Which structures does PA1 make?

Answer 24

maxilla, mandible, zygomatic bone, malleus, incus

Question 25

Which structures does PA2 make?

Answer 25

Stapes, hyoid

Question 26

Which PAs contribute to the heart?

Answer 26

PA3, PA4, and PA6

Question 27

Hox patterning code for PAs

Answer 27

No Hox genes = PA1 Hox2 = PA2 Hox2 + Hox3 = PA3 Hox2 + Hox3 + Hox4 = PA4

Question 28

What happens if Hox2 is deleted?

Answer 28

PA1-like structures are produced by PA2, PA3, and PA4

Question 29

What does ectopic expression of Hox2 in PA1 cause?

Answer 29

Development of PA2-like structures

Question 30

What happens if Hox3 is deleted?

Answer 30

Malformations in PA3 and PA4 only

Question 31

Dlx patterning codes for PA1

Answer 31

``` Dlx1/2 = dorsal (maxilla) Dlx1/2/5/6 = intermediate Dlx1/2/5/6/3/4 = ventral (mandible) ```

Question 32

What is the result of a Dlx1/2 deletion?

Answer 32

Causes problems with maxilla formation

Question 33

What is the result of a Dlx5/6 deletion?

Answer 33

2 maxilla jaws formed as mirror images instead of a maxilla and a mandible

Question 34

Which signalling molecule is important for mandible formation?

Answer 34

Endothelin 1 signalling, as it induces the expression of Dlx5/6

Question 35

What is the result of a KO of endothelin 1?

Answer 35

Dlx5/6 is not induced; therefore, mandible becomes maxilla

Question 36

What is the molecular pathway involving endothelin1, Dlx5/6, Hand1/2, and Bapx1?

Answer 36

Endothelin 1 —> Dlx5/6 —> Hand1/2 —] Bapx1 | Endothelin —> Bapx1

Question 37

What is the function of Bapx1?

Answer 37

Specifies correct position for joint of upper/lower jaw

Question 38

What is the result of ectopic expression of Hand1/2 in maxilla?

Answer 38

Maxilla develops as mandible instead

Question 39

What structures do trunk neural crest cells form? (5 structures)

Answer 39

Neurons (sensory and autonomic), enteric nervous system (controls peristalsis and secretion of digestive enzymes, regulates blood flow and produces dopamine), glial cells, medullary cells of adrenal gland, melanocytes

Question 40

Which cells take neural crest cell path 1 in the trunk?

Answer 40

All neural crest cells (incl. melanocytes)

Question 41

Which cells take neural crest cell path 2 in the trunk?

Answer 41

Only neural crest cells that become melanocytes

Question 42

What type of epigenetic mark is H3K27ac?

Answer 42

Activating mark

Question 43

What type of epigenetic mark is H3K4me2?

Answer 43

Activating mark

Question 44

What type of epigenetic mark is H3K27me3?

Answer 44

Repressing mark