L2: Early Development of CNS

Question 1

Gastrulation starts at day 7. It is important b/c

Answer 1

• forms ectoderm, endoderm, mesodern
• forms midline/primitive streak and notochord
• neural induction (ectoderm knows to become neural ectoderm)

Question 2

1st thing in neurogenesis is

Answer 2

formation of midline/primitive streak

Question 3

At 18 days, neurulation begins by forming the neural plate. The neural plate is formed by?

Answer 3

The neural plate is above the notochord and is formed by neural ectoderm.

Question 4

What kind of effect do bone morphogenic proteins (BMPs) have on neurulation?

Answer 4

BMPs work on the level of transcription to stimulate ectoderm to become epidermis; and NOT neural ectoderm.

Question 5

What does notochord secrete to help with neural induction?

Answer 5

Notochord secretes Chordin and Noggin which will inhibit BMPs and promote ectoderm to become neural ectoderm (neural induction).

Question 6

“default state” of cell

Answer 6

Default state for cell is to become a neuron

Question 7

At 18 days, neural plate forms, then it will invaginate to form a neural groove, then a neural tube. As neural tube forms, neural crest cells pinch off. What are neural crest cells?

Answer 7

they can become give rise to lots of different cells

• cranial neural crest
• trunk neural crest
• vagal and sacral neural crest
• cardiac neural crest

Question 8

the neural tube has a floor plate and roof plate that act as signaling functions. What is highly expressed in notochord & floor plate?

Answer 8

sonic hedgehodge responsible for dorsal-ventral patterning, leading to ventral cell fates

Question 9

Spina bifida

Answer 9

failure of neural tube to close due to folic acid deficiency

Question 10

Ancephaly

Answer 10

no formation of anterior portion of brain due to failure of neural tube to close

Question 11

Holoproencephaly

Answer 11

failure of frontal brain lobes to split at midline due to problems with dorsal ventral patterning

Question 12

Shh pathway can lead to what clinical issues?

Answer 12

1) holoprosencephaly
2) cancers; shh plays a role in cell proliferation
3) cyclopia

Question 13

Cyclopamine

Answer 13

Shh antagonist leading to cyclopia

Question 14

What is highly expressed in the roof plate?

Answer 14

BMPs which will lead to dorsal cell fates

Question 15

Retinoic acid (RA) and fibroblast growth factor (FGF) play a huge signaling role in which pattern pathway?

Answer 15

dorsal-ventral patterning

Question 16

Anterior-posterior patterning overlaps with neural induction. What does A-P patterning result in?

Answer 16

definining the spinal cord, rhombencephelon (hindbrain = pons, medulla, cerebellum), midbrain, proencephelon (forebrain)

Question 17

Which genes play a huge role in A-P patterning?

Answer 17

HOX genes/homeotic genes (particularly impt in hindbrain & spinal cord formation); OTX genes

Question 18

Steps of neural system expansion

Answer 18

• involve both asymmetric & symmetric proliferation
  1. symmetric division makes more neural stem cells (increasing size of of ventricular zone, and size of brain)
  2. early asymmetric division makes 1 neural stem cell, 1 neural precursor
  3. symmetric divisions will eventually lead to 2 neural precursors and less and less pluripotent neural stem cells

Question 19

Where do neurons proliferate and differentiate?

Answer 19

ventricular zones

Question 20

most of gliogeneis occurs after neurogenesis. What are some mechanisms that guide gliogenesis?

Answer 20

astrogliogenesis

• NOTCH will stimulate stem cells to astrocyte precursors
• proneural bHLH will inhibit stem cells to become astrocytes

oligodendrogenesis

• Olig1/2 will stimulate stem cells to become oligodendrocytes
• proneural bHLH will inhibit

Question 21

What is the effect of NOTCH on neurogenesis?

Answer 21

NOTCH signaling will inhibit proneural bHLH, keeping neural stem cells as neural stem cells. Therefore, NOTCH is inhibitory to forming neurons.

Question 22

In presence of another cell’s release of low/mod levels of NOTCH, NOTCH can activate thru delta bHLH genes. What then will happen?

Answer 22

bHLH genes will stimulate neural stem cells to become neural precursors, and then to neurons.

Question 23

When does neurogenesis finish?

Answer 23

middle of 2nd trimester

Question 24

T/F: Defects during 1st 3 weeks are not deadly.

Answer 24

False; it will be deadly b/c neurogenesis normally finishes in middle of 2nd trimester

Question 25

Radial migration

Answer 25

radial migration is how cortex is formed from an inside out manner in which 1st born cells migrate from ventricular zones to pial surface and subsequent cells take same radial migration & migrate above the previous born cells.

Question 26

Reelin mutation

Answer 26

reelin is an ECM protein that helps with radial migration. hence, reelin mutation will lead to lissencephaly(smooth brain)

Question 27

Are interneurons made in the ventricular zones like other neurons?

Answer 27

No, interneruons are made in medial & lateral ganglionic eminences

Question 28

Do interneurons also display radial migration?

Answer 28

No, they migrate tangentially.