Development of the mammalian nervous system

NEU257 1-11-11

-Thousands of cell types

-Trillions of synapses

-Precise connections

Cells & synapses Perception, cognition & behavior

-Billions of cells

Circuits

O’Conner, et al. Nature (2009)

Development sets the spatial and functional contraints that govern nervous system (dis)function

Disease

-within and between areas, structures, nuclei and layers

Approaches to study neural development

1. Descriptive ‘cellular events’A. Prepare tissue from different age specimens

B. Image the same specimen over time

2. Descriptive ‘molecular expression’

A. Protein expression: immunohistochemistry

B. mRNA expression: in situ hybridization

3. “Mechanistic” studies

C. Fate mapping

A. Ablation, transplants (swapping, adding cells/tissues)

B. Gene deletion, overexpression

1. Descriptive ‘cellular events’A. Prepare tissue from different age specimens

Mumm et al., Neuron (2008)

QuickTime™ and aSorenson Video 3 decompressorare needed to see this picture.

1. Descriptive ‘cellular events’B. Image the same specimen over time

Mumm et al., Neuron (2008)

Structures

1. Descriptive ‘cellular events’

C. Fate mapping

Cells

1. Descriptive ‘cellular events’C. Fate mapping

Price et al., JoVS (2009)

2. Descriptive ‘molecular expression’

A. Protein expression: immunohistochemistry

B. mRNA expression: in situ hybridization

Stacey and Wong, JCN (2003)

Shimogori and Grove, Nat Neurosci (2003)

3. “Mechanistic” studies

A. Ablation, transplants (swapping, adding cells or whole tissues)

Sadato labKrubitzer and Kaas, Curr Opin Neurobiol (2002)

B. gene deletion, overexpression3. “Mechanistic” studies

Shimogori and Grove, Nat Neurosci (2003)

The natural experiment of evolution

from: H. Karten

Establishing the raw materials

Cell divisions

Sperm meets egg...

Blastula (ball of cells)

Gastrula (conversion to 3 layers)

Ecto, endo, mesoderm

Nervous system, inner ear, eye

Musclesskeletongonads

circulatory system

liver, lungs, gut, GI tract

From a tri-laminar structure to a folded tube

Gilbert (Developmental Biology)

From a tri-laminar structure to a folded tube

Gilbert (Developmental Biology)

Neural plate, fold and tube in 3-dimensions

Gilbert (Developmental Biology)

Neural crest derivatives

Broad, early rostral-caudal regionalization of the neural plate

Rostral-caudal asymmetries in tube closure timing

Broad arealization of fore-, mid- and hindbrain and rhombomeres

Subdivisions of fore-, mid- and hindbrain, and spinal cord

Dorsal-ventral patterning of the spinal cord: sulcus limitans

Sulcus limitans: sensory versus motor

how far rostral? What does this mean about cortex?

Subdividing major structures into distinct circuits: genetic control: example: rhombomeres

Patterning the forebrain and spinal cord:similar themes

Cell division, migration and cortical expansion

Cell division, migration and cortical expansion

Birthdating (cellular fate mapping) in the neocortex“Inside-out” neurogenesis

Rakic

Tangential migration of interneurons from distant origins (in the same brain)

Combining approaches: molecular expression, fate mapping, anatomy and physiology

Miyoshi et al., J Neuroscience (2010)

Combining approaches: molecular expression, fate mapping, anatomy and physiology

Miyoshi et al., J Neuroscience (2010)

Connecting one area to the next

Axons in one brain area head toward their targets in another brain area via intermediate cues that can

be both attractive or repulsive

Once they find their targets, they know where to go within their targets according to gradients of

attractants and/or repellants

How they pick which overall targets or specific cells to connect to remains a mystery