Steps in setting up the Nervous system• Induction and Patterning of a neuron-forming region• Birth and migration of neurons and glia• Specification of cell fates• Guidance of axonal growth cones to specific targets• Formation of synaptic connections• Binding of trophic factors for survival and differentiation• Competitive rearrangement of functional synapses• Continued synaptic plasticity during lifetime

Neuronal development• Ectoderm differentiation: Epidermis, nerve tissue, or neural

crest cells?• Nerve tissue: Neuron or glial cell?

Neuronal development• Ectoderm differentiation: Epidermis, nerve tissue, or neural

crest cells?• Nerve tissue: Neuron or glial cell?

Neuronal development

Nerve Outgrowth• Filapodia-based movements• Rely on Cytoskeleton and factors that rearrange the

cytoskeleton (GTPases).

Types of Tissue organization in the Neural Tube

Spinal Cord

Cerebellum• Important for motor control• Purkinje fibers• BMP and Granular layer

Movement of Neurons• Glial cells serve as track.• Nerve Birthdays: Determine how deep in the cortex a neuron

will enter.

Cerebrum• Similar to Cerebellum• Neocortex: subdivided into

6 layers (old cells closest to ventricular zone).

• Cortex divided horizontally (approx. 40 sections).

• Fate decided early on (before S phase)

Cortical Neurons

Spinal Cord

Motor Neuron Specification• Sonic hedgehog (Shh) secreted by floor plate.

Target specification of Motor neuron• As Nerves pass through the cortex, different transcriptional

regulators are expressed.• Limb innervation determined by repulsion

– If Lim1 is present, Eph A4 (receptor) is expressed; Eph A5 repels neuron– If no Lim1, neuropilin-2 expressed.

(Axial muscles)

Following diffusible signals• Netrin-1 and Netrin-2• SLIT and ROBO

Nerve Outgrowth• Filapodia-based movements• Rely on Cytoskeleton and factors that rearrange the

cytoskeleton (GTPases).

Finding a place to hang out

Neural Crest Cells• Neurons/glial cells of

sensory, sympathetic, and parasympathetic nerves

• Epinephrine-producing cells of adrenal gland

• Pigment containing cells• Skeletal/connective tissue

of head

• 4th germ layer?

Ventral Migration of Neural Crest

Neural Crest Cell specification

Neural Crest Regionalization• Cranial

– Cartilage, bone, cranial nerves, glia, connective tissues

• Cardiac– Melanocytes, neurons,

cartilage, musculo-connective tissue wall of large arteries

• Trunk– Dorsal root ganglia,

sympathetic ganglia, adrenal medulla, nerve clusters around aorta

• Vagal and Sacral– Parasympathetic ganglia of gut

Trunk Neural Crest Cells: Migration• Dorso-lateral inhibited• At first, between somites,

but Semaphorin-3F causes movement through somites.

Further migration• Cells that stop in sclerotome-

dorsal root ganglia• Cells past sclerotome-lack wnt

and neurotropin receptors- parasympathetic and sympathetic nerves.

• BMPs from aorta convert cells to sympathetic and adrenal lineage

• Glucocorticoids- adrenomedullary cells.

• Neural crest cells committed to path early, but differentiate to determine final location.

Cranial Neural Crest• Head is most anatomically sophisticated portion of vertebrate

body.• Mainly composed of neural crest cells

Cranial Neural Crest: Bone Formation

Neural Crest and neurocranium• Viscerocranium (jaws, pharyngeal arches) well established as

being of Neural crest origin…neurocranium controversial origin

The Face reflects the brain!

Cardiac Neural Crest

Cranial placodes