Stem Cells and Neuronal Progenitors and Their Diversity in the CNS: Are Time and Place Important?

Abstract

Stem cells are multilineage progenitor cells that are capable of self-regenerating and giving rise to different cell types. The proper assembly of the CNS into functionally relevant circuits requires that stem cells produce the right types of cells in the right number and position at the appropriate time. We suggest that the positional specification of stem cells is provided by the pattern of expression of early transcriptional regulators along the body axes. These mechanisms restrict the competence of stem cells to programming a local cellular repertoire. Conversely, we argue that the specification of different cell types in the appropriate number and sequence is independently carried out within CNS domains by subprograms that progressively change the intrinsic properties of the stem cells. Temporal changes in proliferation and differentiation of stem cells are controlled by cascades of extracellular signals and basic helix-loop-helix (bHlH) transcription factors. These regulators in turn may activate homeodomain transcription factors with more restricted effector functions. Fibroblast growth factors (FGF) are among the earliest acting signals providing local changes in growth within the developing CNS. Basic FGF (FGF2) increases the proliferation of either stem cells or their immediate progeny, increasing the number of founder cells in the developing cerebral cortex.

Keywords

Stem cells Fibroblast growth factor FGF Homeodomain genes Neurogenesis Cerebral cortex

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