DEVELOPMENT OF THE CNS II Key points Factors that influence cell lineage and differentiation Migration of cells Growth of processes and recognition of target cells Maps and polarity gradients Regressive events including cell death and pruning of axons Reading – NB these texts mostly describe embryology and do not discuss cellular developmental events Nolte (4th Ed), pgs 36-49 Fitzgerald, pgs 1-7 Crossman and Neary, pgs 3-8 Kiernan, pgs 4-11, 39-40

Specification of the neural tube and neural crest 22-23 days

Cell lineage and differentiation Stem cells What controls the differentiation of stem cells into neurons and glia? What are the lineage relationships between different classes of neurons and glia? When does a cell become committed to a particular phenotype?

Radial migration in the developing telencephalon

Inside-out sequence of birthdays Migration Inside-out sequence of birthdays

Axon outgrowth and target recognition Growth cones Substrate guidance Polarity markers and formation of specific connections

Guidance of growing axons Diffusible and contact mediated factors – attraction and repulsion

Regressive events Cell death Growth or trophic factors Elimination of axons Loss of synapses

Retrograde influences on neuronal viability and phenotype

Dendritic spines and synaptic density – changes with age HUMAN Dendritic spines and synaptic density – changes with age