Developmental Genetics of the Human Brain

Question 1

What is the most common way of imaging the fetus in vivo?

Answer 1

MRI, ultrasound.

Question 2

Telencephalon

Answer 2

“Furthest brain”; Cortex

Question 3

Rhombencephalon

Answer 3

Brainstem.

Question 4

Seven stages of development

Answer 4

1. Gastrulation
2. Primary Neurulation
3. Prosencephalic development
4. Neuronal proliferation
5. Neuronal migration
6. Organization
7. Myelination

Question 5

What occurs in gastrulation

Answer 5

Cells differentiate into three layers: endoderm, mesoderm, and ectoderm.

Question 6

Which layer formed in gastrulation develops into neural tissue?

Answer 6

Ectoderm layer.

Question 7

What occurs in primary neurulation?

Answer 7

Ectodermal layer folds into a tube structure.
BMP dorsal secretion and SHH ventral secretion lead to gradient inducing differentiation of ectodermal cells into neuron subtypes.

Question 8

Where is SHH secreted from?

Answer 8

Notochord

Question 9

Which side of the neural tube closes first?

Answer 9

Anterior pore.

Question 10

What is the result of the anterior pore closure defect?

Answer 10

Anencephaly; lack of development and organization in brain.

Question 11

What is the result of posterior pore closure defect?

Answer 11

Spina bifida.

Question 12

What occurs in prosencephalic development?

Answer 12

Anterior neural tube divides into prosencephalic vesicles.
Specializes into 3 vesicles: forebrain, midbrain, hindbrain, and spinal cord.
Further specializes into telencephalon, diencephalon, mesencephalon, metencephalon, and mylencephalon.

ALSO FORMATION OF BRAINSTEM

Question 13

Diencephalon

Answer 13

“Inter” brain

Question 14

Telencephalon

Answer 14

“Far” brain

Question 15

Mesencephalon

Answer 15

“Mid” brain

Question 16

Metencephalon

Answer 16

“Behind” brain

Question 17

Mylencephalon

Answer 17

“After brain”

Question 18

What structures are in the forebrain?

Answer 18

Telencephalon and diencephalon

Question 19

What structures are in the midbrain?

Answer 19

Mesencephalon

Question 20

What structures are in the hindbrain?

Answer 20

Metencephalon and Mylencephalon

Question 21

Holoprosencephaly

Answer 21

A condition resulting from a defect in the prosencephalic development stage. The neural tube does not divide or differentiate into different structures.

Results in low cognitive functioning, hypotonia, and/or microcephaly.

Question 22

Hypotonia

Answer 22

Decreased muscle tone

Question 23

Microcephaly

Answer 23

Decreased brain size

Question 24

What is a REUSED gene associated with holoprosencephaly?

Answer 24

SHH gene

Question 25

SHH pathway

Answer 25

Interaction with patched and smoothened receptors activate messenger GLI that results in transcription and proliferation.

Question 26

Mobius Syndrome

Answer 26

Faulty development of brainstem in the procephalic development stage that results in improper cranial nerve (3, 6) function. Results in congenital partial or complete facial diplegia. As well as malformation of the limbs.

Question 27

Equinovarus

Answer 27

Malformation of limbs

Question 28

What is the cause of diseased brainstem development?

Answer 28

HOXb1 and Hoxb4 genes

Question 29

What animal was used in the HOX gene research? What were the results of this research?

Answer 29

drosophila; learned that there are very similar genetic organizations in HOX genes.

Question 30

What occurs in neuronal proliferation?

Answer 30

Thickening of brain tissue due to cell proliferation.

Question 31

Hemi-megalencephaly

Answer 31

Condition due to excessive cell proliferation in neuronal proliferation development stage: macrocephaly or hemi-macro cephaly.

Question 32

Tuberous sclerosis

Answer 32

A disease of skin and brain due to abnormal cell proliferation in neuronal proliferation developmental stage. Intellectual disability, autism.

Question 33

What is tuberous sclerosis associated with/caused by?

Answer 33

Mutations in TSC1 or TSC2.

Question 34

Tuberous sclerosis tumors

Answer 34

Subependymal giant cell astrocytoma 9SEGA) that forms in the ventricular wall and causes improper drainage resulting in high pressure. Often results in a fatality.

Question 35

What does lack of proliferation result in?

Answer 35

Microcephaly

Question 36

What do FOXG1 mutations cause?

Answer 36

Microcephaly

Question 37

What occurs in neuronal migration?

Answer 37

Cortex is divided into 6 layers via migration of neurons from ventricular cell walls.

Question 38

How do neurons migrate?

Answer 38

Neurons are born in the periventricular zone and are guided by undifferentiated "guide" cells that pull neurons out to their respective cortical regions.

Question 39

What type of migration occurs in neuronal migration?

Answer 39

Inside-out

Question 40

Periventricular Nodular Heterotopia

Answer 40

Improper migration of neurons in neuronal migration stage. Characteristically large ventricles with unregulated periventricular cells. Results in epilepsy and cognitive dysfunction

Question 41

What genetic mutations cause PNH

Answer 41

Filamin 1 ARFGEF 2 Elastin (William's syndrome) Fragile X Syndrome

Question 42

What genetic interaction results in PNH

Answer 42

Filamin and Fragile X

Question 43

Lissencephaly

Answer 43

Improper migration results in a lack of gyri and sulci.

Question 44

What genes are associated with Lissencephaly

Answer 44

``` LISI 14-3-3 varepsilon Doublecortin Reelin ARX ```

Question 45

What occurs in the organization stage?

Answer 45

Neurite outgrowth; dendrites and axons overlab and lead to increased branching. Formation of dendritic spines.

Question 46

What diseases are associated with abnormal dendritic arbor/spine

Answer 46

Down syndrome Fragile X Angelman ID and ASD

Question 47

Fragile X Syndrome

Answer 47

Most common ID in males Dysmorphic features Autism/Epilepsy Mutation in Fragile X gene leading to absence of Fragile X protein

Question 48

What does an absence of Fragile X protein result in

Answer 48

Fragile X Syndrome | Long and skinny dendritic spines, poor neurotransmission

Question 49

What are 2 functions of glia?

Answer 49

Recycling of glutamate into glutamine | Regulation of Calcium flux

Question 50

What occurs in the Myelination stage?

Answer 50

Glia proliferation

Question 51

What does myelin allow?

Answer 51

Saltatory conduction, increased AP