Subset of early radial glial progenitors that contribute to the development of callosal neurons is absent from avian brain

Abstract

The classical view of mammalian cortical development suggests that pyramidal neurons are generated in a temporal sequence, with all radial glial cells (RGCs) contributing to both lower and upper neocortical layers. A recent opposing proposal suggests there is a subgroup of fate-restricted RGCs in the early neocortex, which generates only upper-layer neurons. Little is known about the existence of fate restriction of homologous progenitors in other vertebrate species. We investigated the lineage of selected Emx2 + [vertebrate homeobox gene related to Drosophila empty spiracles (ems)] RGCs in mouse neocortex and chick forebrain and found evidence for both sequential and fate-restricted programs only in mouse, indicating that these complementary populations coexist in the developing mammalian but not avian brain. Among a large population of sequentially programmed RGCs in the mouse brain, a subset of self-renewing progenitors lack neurogenic potential during the earliest phase of corticogenesis. After a considerable delay, these progenitors generate callosal upper-layer neurons and glia. On the other hand, we found no homologous delayed population in any sectors of the chick forebrain. This finding suggests that neurogenic delay of selected RGCs may be unique to mammals and possibly associated with the evolution of the corpus callosum.S everal neural progenitor subtypes have been identified in the developing mammalian neocortex (1-4). At the onset of neurogenesis, multipotent proliferative radial glial cells (RGCs) reside at the ventricular surface. RGC divisions can be "self-renewing," a symmetrical division in which two identical RGCs are generated; "direct neurogenic," generating a neuroblast and a multipotent progenitor; or "indirect neurogenic," which gives rise to an intermediate progenitor that migrates to divide in the subventricular zone. The timing of these events is crucial for cell number and fate determination (5-7) and vary among different mammalian species. Importantly, very little is known about the homologous populations of RGCs in other vertebrate species and about their role in cortical evolution.Observations made from Golgi-stained material (4, 8), birthdating (5, 9), and lineage-tracing analysis (10-14) contributed to the formation of the "sequential" hypothesis. Accordingly, each RGC in the early brain generates most cortical cell types by sequential mitoses (15). Long-range subcortical projection neurons of the deep layers are generated first, followed by the callosal projection neurons of the upper layers, and finally the glial cells (16).However, recent genetic fate mapping of selected lineages has revealed a subpopulation of early RGCs expressing Cux2, which only gives rise to Satb2-positive upper-layer cortical neurons (17). This finding suggests that the early neurogenic brain may contain several types of cortical progenitors, each of which constrained to generating certain subpopulations of neurons, known as the "restricted progenitor hypothesis" (18). The existence of these restricted ...

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