Neurodevelopment

Question 1

What is the general order and transformation of neural stem cells in developing brain?

Answer 1

• Cells that can generate neural tissue or are derived from the nervous system, have self-renewal, and can give rise to other cells through asymmetric cell division.
• Zygote (non-self-renewing) totipotent, embryonic stem cell (self-renewing) pluripotent, multipotent stem cells (neuroepithelial cells), neural progenitor (radial glial cells), committed neurol progenitor (neural or glial)neuron or glia
• Proteins determine what type of cell comes from asymmetric division

Question 2

Describe the various ways radial glial cells contribute to brain development

Answer 2

• Radial glial cells make most of the neurons and glia, possibly oligodendrites, this happens during the embryo stage. During birth they start to make astrocytes then the forming adult brain begins to make ependymal cells, b-cells, and other cell types.

Question 3

Describe the origins of major neuronal subtypes in formation of the cortex and cerebellum

Answer 3

• Deep cells in the cerebral cortex (in white matter) are born first, as more are born they travel up to form six cortical layers. Most inhibitory neurons are born in the basal forebrain (medial ganglionic eminence) while excitatory neurons are born in the ventricular zone.

Question 4

What are the different modes and patterns of neuronal migration

Answer 4

• Inhibitory neurons migrate tangentially, parallel to the ventricular surface. Excitatory neurons use glial fibers to migrate out towards the outer layers of the brain The cerebellum in mice forms on the roof of the fourth ventricle. The ventricular zone makes Purkinje cells (pink). Granular cells (purple) are made in the rhombic lib and migrate across the surface of the cerebellum where they are regulated by the Purkinje cells. The Purkinje cells release factors like Sonic HedgeHog (SHH) to the granular cells, causing them to mature. As they mature, the granular cells move past the Purkinje cells and eventually reside beneath the Purkinje layer. This cell location swap occurs at around 30 weeks in gestation and continues until about 6 months after birth (in humans).

Question 5

How do genetic mutations during neural development lead to various types of brain malformations

Answer 5

• Genes and proteins guide the migration of cells. They also stimulate actin and microtubule polymerization which is needed to form cortical areas. When these genes are dysregulated, the centrosome gets lost and cannot travel or goes to the wrong area as it does not have a guide. This leads to improper build-up of cells. Abnormal Spindle-like microcephaly-associated (ASPM) mutations
Microtubule mutation that reduces cell proliferation
Brain is smaller
Hyperproliferation
Hemimegalencephaly and Megalencephaly
Accelerates cell proliferation and causes the brain to be larger
Beta-catenin overexpression in mice causes cells to speed up cell cycle exit and overproduce. The proliferative zone is expanded and animals die at birth. Causes mouse brain to look more gyrated (similar to human brain).
Sonic HedgeHog (SHH) mutation leads to medulloblastoma

Question 6

Compare and contrast symmetric and asymmetric divisions

Answer 6

Symmetric division: mitoses that give rise to cell types of similar fate. Asymmetric: mitoses that give rise to cell types of different fates.

Question 7

Describe fate determinants during mitosis

Answer 7

Proteins are fate determinants. they segregate complexes in the neuroblast. Examples: numb, numb like, aPKC, Bazooka