Role of Intermediate Progenitor Cells in Cerebral Cortex Development

Abstract

Intermediate progenitor cells (IPCs) are a type of neurogenic transient amplifying cells in the developing cerebral cortex. IPCs divide symmetrically at basal (abventricular) positions in the neuroepithelium to produce pairs of new neurons or, in amplifying divisions, pairs of new IPCs. In contrast, radial unit progenitors (neuroepithelial cells and radial glia) divide at the apical (ventricular) surface and produce only single neurons or single IPCs by asymmetric division, or self-amplify by symmetric division. Histologically, IPCs are most prominent during the middle and late stages of neurogenesis, when they accumulate in the subventricular zone, a progenitor compartment linked to the genesis of upper neocortical layers (II–IV). Nevertheless, IPCs are present throughout cortical neurogenesis and produce neurons for all layers. In mice, changes in the abundance of IPCs caused by mutations of Pax6, Ngn2, Id4 and other genes are associated with parallel changes in cortical thickness but not surface area. In gyrencephalic brains, IPCs may play broader roles in determining not only laminar thickness, but also cortical surface area and gyral patterns. We propose that regulation of IPC genesis and amplification across developmental stages and regional subdivisions modulates laminar neurogenesis and contributes to the cytoarchitectonic differentiation of cortical areas.

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

“…Cortico-cerebral histogenesis is an extremely complex process, characterized by a well-defined spatial [1][2][3][4][5], temporal [6], and histogenetic plan [7]. Precursors giving rise to mature cell types include neural stem cells (NSCs), able to self-renew indefinitely and to generate all the mature cell types; and NSC-derived, lineage-restricted progenitors, characterized by more limited self-renewal potentials and more restricted histogenetic potencies.…”

“…Neuronal-restricted progenitors (NPs) include apical short neuronal precursors/''pin-like'' cells, within the VZ, and basal intermediate precursor cells, in both VZ and subventricular zone (SVZ). Bipotent glial-restricted progenitors (hereafter referred to as glial progenitors [GPs]) generate both astrocytes and oligodendrocytes [7][8][9][10][11][12][13][14][15].…”

RP58/ZNF238 directly modulates proneurogenic gene levels and is required for neuronal differentiation and brain expansion

“…1-3 INPs divide 1-2 times and only give rise to neurons, with regulation of their number proposed to contribute to cortical expansion. [1][2][3][4][5][6] Molecularly, a sequence of key transcription factors, Pax6-4Ngn2-4Tbr2-4NeuroD1-4Tbr1, promotes cortical neurogenesis. 7 Among these, Ngn2 is required for transition from early Pax6 þ radial glia to Tbr2 þ INPs, as well as for expansion of INPs, whereas NeuroD1 is expressed in INPs and early-differentiating neurons.…”

“…Two main types of precursors exist in the developing neocortex: multipotent radial glial stem/progenitor cells (RGCs) in the ventricular zone (VZ) and derived intermediate neurogenic progenitors (INPs) in the subventricular zone (SVZ). [1][2][3] INPs divide 1-2 times and only give rise to neurons, with regulation of their number proposed to contribute to cortical expansion. [1][2][3][4][5][6] Molecularly, a sequence of key transcription factors, Pax6-4Ngn2-4Tbr2-4NeuroD1-4Tbr1, promotes cortical neurogenesis.…”

Reprint of “The clinical impact of deficiency in DNA non-homologous end-joining”

“…The embryonic neuronal stem and progenitor cells are located in the ventricular and sub-ventricular zones (VZ-SVZ) which lie adjacent to the ventricular membrane [91,92]. Adjacent to the VZ-SVZ is the intermediate zone (IZ) with the cortical plate (CP) representing a distal layer observed during later stages of neurogenesis.…”