Lecture 2: Early Brain development

Question 1

The invagination of the blastula gives rise to the three premortal germ layers. What are they?

Answer 1

Mesoderm, Endoderm, Ectoderm

Question 2

What is the mesoderm grown into?

Answer 2

Skeletal, muscular and cardiovascular systems

Question 3

What is the endoderm grown into?

Answer 3

urinary, digestive and respiratory systems

Question 4

What is the ectoderm grown into?

Answer 4

skin (epidermis) and nervous systems

Question 5

Skin cells communicate very much like nerve cells. True or Not

Answer 5

True

Question 6

What is Neurulation?

Answer 6

Invagination of the ectoderm dorsally, the neural plate, which separated from
the ectoderm. It will form a tube inside the embryo.
- Thus, the neural plate forms the neural tube which will become the CNS.
- The notochord which is part of the mesoderm is the structure that makes the
neurulation happen and will become the vertebral column.

Question 7

What does the neural tube become?

Answer 7

CNS (brain and spinal cord)

Question 8

What does the notochord become?

Answer 8

Vertebral column

Question 9

What does the neural crest become?

Answer 9

peripheral nervous system

Question 10

What are the most important part of the peripheral nervous system?

Answer 10

Sensory ganglia which are
located just outside the spinal cord.

Question 11

Where do autonomic ganglia originate from?

Answer 11

Autonomic ganglia also originate from neural crest cells
as do adrenal chromaffin cells and melanocytes.

Question 12

At 20 days you can see the invagination of the neural plate clearly, It takes place from themiddle of the embryo and then extends to the head and tail region. At 47 days the neural tube is formed. Is this statement True or False?

Answer 12

False, at 22 days the neural tube is formed.

Question 13

What is spina bifida?

Answer 13

No closure of the ectoderm leaving some of the neural tube exposed

Question 14

What is Anencephaly?

Answer 14

(without a brain). ectoderm did not close in the head region causing no
proper brain development, they survive during pregnancy but die at birth

Question 15

What is the term Exencephaly?

Answer 15

Brain develops outside of the embryo, they can also not survive outside of
the womb.

Question 16

What are the Extrinsic inductive signals called?

Answer 16

Morphogens

Question 17

Where are these Morphogens produced?

Answer 17

Extrinsic inductive signals (morphogens) are produced by surrounding cells (tell the neural
system how to develop (brain part, spinal cord part))

Question 18

Give us three examples of morphogens?

Answer 18

Chordin, noggin, bone morphogenic proteins (BMPs),
Wnt, fibroblast growth factor (FGF), Retinoic acid (RA), Sonic hedgehog (Shh), etc.

Question 19

What is the function of a morphogen?

Answer 19

It changes intrinsic gene expression by inducing expression of transcription
factors.
– Hox, Pax, Msx, Olig, Sox, Snail, bHLH, etc.

Question 20

What are Hox genes?

Answer 20

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals.

Question 21

Retinoic acid can come into the cell while others need a membrane receptor. They often use tyrosine kinase receptors or G-protein receptors causing intracellular cascade to eventually signal to the nucleus.
Are these statements True or False?

Answer 21

True

Question 22

Inductive signals act as teratogens. What are teratogens?

Answer 22

Agent that causes malformations in embryos

Question 23

How is too much gene expression activated?

Answer 23

Small Amounts of maternally supplied RA.

Question 24

What do these morphogens (like Shh and Noggin) determine?

Answer 24

The directional development of the brain.

Question 25

Every cell that turns blue responds to retinoic acid causing too much gene expression and
abnormalities like no midline in the brain (no left and right side). Is this statement True or False?

Answer 25

True

Question 26

The spinal cord is organized in the dorsoventral specification? What is there in dorsal side and what is there in the ventral side?

Answer 26

• Dorsal side: sensory inputs
• Ventral side: motor neurons

Question 27

The very same structure that is used to induce neurulation, the notochord, also plays a role in dorsoventral specification. What does it produce?

Answer 27

It produces the morphogen Sonic hedgehog (Shh)

Question 28

Why does it create a concentration gradient with high Shh on the ventral side and a low concentration at the dorsal side.

Answer 28

The ventral to dorsal Shh gradient defines the patterning of the ventral neural tube into 5 domains (V0, MN, V1, V2, V3). The cells respond differently to high and low
concentrations of Shh causing dorsoventral specification.

Question 29

Why does the opposite happen with Noggin compared to Shh?

Answer 29

Noggin, also known as NOG, is a protein that is involved in the development of many body tissues, including nerve tissue, muscles, and bones. In humans, noggin is encoded by the NOG gene. Noggin and noggin-like genes control dorsoventral axis regeneration.

Question 30

The 39 human HOX genes are located in four clusters (A-D) on different chromosomes. Is this statement True or False

Answer 30

True

Question 31

What is Hensen’s node?

Answer 31

A group of cells that acts as an organizer of development in the early embryo of birds and mammals. It is located immediately anterior to the primitive streak and is analogous to the dorsal lip of the blastopore in the blastula of an amphibian embryo.

Question 32

The genes in the anterior part are sensitive to low concentrations of Retinoic acid. This
causes differential expression of HOX genes.
* This concentration should be well controlled.
* Hensen’s node is the only place where RA is produced in the embryo (not in adult).
* Hensen’s node can move from the anterior side to the posterior side and grows while
doing this.
A. All three are untrue
B. All three are True
C. I is True, II is not True, III is True
D. II is True, I is not True, III is not True

Answer 32

B

Question 33

What are the six forebrain segments called?

Answer 33

Prosomeres

Question 34

What are eight hindbrain segments called?

Answer 34

Rhombomeres

Question 35

The brain develops from a tube-like structure. It really grows and extends in the radial direction. The spinal cord divides into 7 segments

Answer 35

False, 31 segments

Question 36

Give some of the characterizations of neural stem cells?

Answer 36

– are multipotent (i.e. they can become neurons
or glia)
– have unlimited capacity for cell division
– are self-renewing (i.e. they always generate new
stem cells) (one differentiates and the other does
not)

Question 37

Microglia are immune cells and are not made from ectoderm! → extroembryonic mesoderm orgin (yolk sac macrophages).
True or False

Answer 37

The statement is True

Question 38

Give us the characterization of Ventrical Zone compared to the Subventrical Zone?

Answer 38

Ventricular zone and subventricular zone are transient fetal proliferative zones where progenitor cells for all future cortical neurons and macroglia reside and exponentially expand progenitor population by symmetric cell division.
Astrocytes residing in the SVZ have been shown to spawn migratory neuroblasts via transitory amplifying progenitor cells. These migratory neuroblasts play a role in maintaining the olfactory circuitry in healthy brains and potentially have restorative properties after brain injury.

Question 39

SubVZ in Dorsal and ventral horn of lateral ventricles have different function. What are the functions?

Answer 39

• Dorsal → smell neurons for olfactory, olfactory easily dies.
• Ventral → makes neurons for hippocampus, needed for learning and memory.

Question 43

What is microcephaly?

Answer 43

Microcephaly is an abnormality of the central nervous system in which the skull size is too small. It is usually a congenital condition. The brain does not develop properly so the skull also remains smaller. Often there is intellectual disability.

Question 44

What is Lissencephaly?

Answer 44

Lissencephaly is a congenital brain disorder that is very rare. Lissencephaly literally means “smooth brain.” There are many different variants and syndromes. Miller-Dieker syndrome, Walker-Warburg syndrome and Fukuyama syndrome are a few examples.

Question 45

What is Inverted cortical layering?

Answer 45

In the absence of reelin or its receptors, the process of neuronal migration is compromised, which causes severe abnormalities in cortical lamination. The resulting phenotype was initially described as an inversion of the layers, whereby the normal “inside out” pattern was inverted into an “outside in” pattern.

Question 46

What is cobblestone cortex

Answer 46

In Classical lissencephaly the cortex becomes thickened and can be identified by four layers of the cerebral cortex rather than six. Cobblestone lissencephaly is named after the pebbled or cobblestone appearance of the cortical surface

Question 46

What is Walker-Walkburg syndrome

Answer 46

Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past childhood.

Question 47

What is Pleiotropism?

Answer 47

Pleiotropism (πλείων = more): the control by a single gene of several distinct and seemingly unrelated phenotypic effects

Question 48

What happens when both RA and Shh are activated and something went wrong in the signalling?

Answer 48

The midline (left/right brain side) is not so good -> holoprosencephaly

Question 49

What happens if uncontrolled Shh keeps going on?

Answer 49

The most common thing that will happen is a brain tumor.

Question 50

What happens when there is too much Shh in skin cells?

Answer 50

Basal cell carcinoma