Early brain development 2

Question 1

Lumen

Answer 1

Part of the neural tube that eventually forms the ventricles in the brain

Question 2

Neural tube defects

Answer 2

Spinal bifida well know example
Caused by nutrient deficiency
Folic acid = disrupts adequate formation of the neural tube
Vitamin A - precursor of RA, leads to impaired development of the neural tube

Question 3

Cell differentiation

Answer 3

Occurs in neural tube and later in specialized sites in the brain
Divide into three types = neurons, astrocytes and oligodendrocytes

Question 4

Neural stem cells

Answer 4

Multipotent (can become neurons or glia cells)
Have unlimited capacity for cell division
Self renewing

Question 5

Asymmetrical division

Answer 5

Stem cell divides into new stem cell and progenitor cell.
Progenitor cell can further divide in neuroblast and new progenitor, but with limited potential. Neurol progenitor cell is called neuroblast: can no longer become astrocyte of oligodendocyte progenitor and vice versa.

Question 6

Neuroblast and glioblast cells

Answer 6

• point of no return
• Limited capacity for cell division
• Neuroblast cells develop into neurons

Question 7

Ventricular Zone

Answer 7

Neuroepithelial stem cells along lumen of ventricles
Cells only active during prenatal development

Question 8

neurogenesis in the prenatal brain

Answer 8

At late stages precursor cells mostly disappear and few new neurons are generated. Neurons that dies because of age or injury cannot be replaced

Question 9

Subventricular zone

Answer 9

Generates neurons that migrate to the olfactory bulb (smell)

Question 10

Subgranular zone

Answer 10

Generates neurons that migrate into the hippocampus (learning and memory)

Question 11

Dopamine

Answer 11

Midbrain dopamine neurons originate from the ventricular zone (VZ) in the floor plate of neural tube

Inductive signals and transcription factors define final destination and subtype of dopamine neurons

Loss of dopamine causes parkinsons

Question 12

Lissencephaly - cell migration deficit

Answer 12

Ventricle enlarged
White mater nearly absent
Sulci and gyri completely absent

Causes seizures and mental retardation
2 - 20 years life expectancy

Question 13

Radial migration in the cortex

Answer 13

Final localization of neurons in the CNS depends on radial migration of neuroblast cells.
Guided by radial glia cells.
Neuroblast cells travel along the radial processes to their final destination and then further differentiate into their final neuronal subtype.
Neocortex: six layers with distinct cell-types and cell morphology
Layering in inside-out manner.
Starts with deep layers (6-5) and then cells travel through these deep layers to form the superficial layers.
Layering is also determined by differences in gene expression regulated by TFs

Question 14

Cortical migration defects

Answer 14

Mutations in genes coding for proteins involved in migration
-Cell-adhesion molecules
-Microtubule binding proteins

Question 15

Deficit specifications

Answer 15

Initiation defect: partial migration. Microcephaly or small brains
Ongoing migration defect: impaired layering of the cortex. Lissencephaly
Lamination defect: inverted layering
Stop signal defect: cells migrate to far. Enlarged brain

Migration defects result in gross malformations of the brain

Question 16

Deficit examples

Answer 16

Reelin mutation - lamination defect:inverted layering
Lissencephaly: DCX mutation, ongoing migration defect - impaired layering of cortex
Double cortex: subcortical band, enlarged brain
Cobblestone cortex: enlarged brain and loss of gyri and sulci. Stop signal defect

Question 17

Neuroblast cells and neurites

Answer 17

Dendrites receive signal
Axon sends signal
When neuroblast have reached their final destination, they will develop into neurons.
Neurons are a highly specialized form of polarized cells.

Initially, neuroblast cells develop neurites. Neither axon nor dendrites.
Similar to regional patterning and cell differentiation, transcriptional programs determine which neurite becomes an axon.
Neurites and especially axons are characterized by growth cones present at their tips.

Question 18

Axons (microtubules) and growth cones (actin bundles)

Answer 18

GCs explore the extracellular environment and thereby determine the direction of growth.
Axon elongation is mediated by the microtubule cytoskeleton. Essential for structure and transport of proteins.
Growth cone dynamics are mediated by the actin cytoskeleton, which form small filopodia.
Filopodia are like fingers sensing the environment.

Question 19

Filopodia

Answer 19

Growth cones and their filopodia are highly dynamic.
Come and go within order of minutes or even seconds.
Filopodia retract or extend depending on extracellular signals.
Rapid breakdown and extension of the actin cytoskeleton in filipodia.