55-140 Lecture Notes - Neurogenesis, Commissure, Bone Morphogenetic Protein 4

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Outline of Lecture 11 (02-20 D; Ghosh)
Development II
I. Neural induction: the notochord plays a key role
A) Quick review
- During gastrulation, dorsal tissue migrates through blastopore lip to become mesoderm
- Notochord forms from mesoderm, and induces ectodermal neural plate formation
B) Neural induction
- Default fate of ectodermal cells is neuronal; BMP4 induces epidermal fate
- Notochord produces noggin, chordin to inhibit BMP4, thereby inducing neural diffn
- Notochord produces Shh a ventralizing morphogen that acts in a graded manner: high Shh (most
ventral) induces motoneurons, intermediate induces interneurons, low produces
commissural neurons
- Roof plate produces BMP2, a dorsalizing morphogen
- Neurons are produced by lateral walls of neural tube, NOT the roof or floor plate
II. Neurogenesis
A) Ventricular zone: site of neurogenesis
- Asymmetric divisions (parallel to base) give rise to neurons, whereas symmetric divisions
(perpendicular to base) do not
- Neurons are generated early and glial cells are generated later
- Neuroblasts divide only 1-2 times before diffn into neurons
- Glioblasts divide many times before diffn, fewer glioblasts needed than neuroblasts
- Signal through notch receptor inhibits neural development; this may be a way cells decide to
diffn into neurons (cell with delta ligand becomes neuronal; cell with notch receptor
remains nonneuronal)
B) Intermediate zone: postmitotic neurons migrate through this layer
- Neurons that migrate radially along the processes of radial glial cells to the CP to
become excitatory neurons
- Neurons that migrate tangentially (e.g. from ganglionic eminences) become inhibitory
interneurons
C) Cortical plate: where postmitotic neurons come to rest
- Cortical plate consists of 6 layers (1st is most superficial)
- Neurons populate each layer sequentially starting with layer 6, ending with layer 1
- The laminar fate of a cell is decided between S and M phase
Summary of major points
- Understand the role of noggin, chordin, BMP4, Notch
- Understand how neuronal cells develop differently: e.g. how does induction, cell division,
migration, timing affect/correlate with neuronal differentiation
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