Abstract
Author SummaryPatterning of the cerebral cortex occurs early during embryonic development in response to secreted molecules or morphogens produced at signaling centers. These morphogens establish the graded expression of transcription factors (TFs) in progenitor cells and control the size and positioning of cortical areas in the postnatal animal. CR cells are among the earliest born cortical neurons and play a crucial role in cortical lamination. They are generated at signaling centers and migrate over long distances to cover its entire surface. We show that three different CR subtypes distribute in specific proportions in cortical territories. Genetic ablation of one subpopulation leads to a highly dynamic redistribution of the two others. This results in defects in expression of transcription factors and in progenitor cell proliferation, which correlate with the resulting changes in the size and positioning of cortical areas. Given our additional evidence that CR subtypes express specific repertoires of signaling factors, the ablation phenotypes point to a novel early role for CR cells as mediators of cortical patterning and suggest that CR cells are able to signal to progenitor cells. Our data thus add to the conventional model that morphogens act by passive diffusion and point to a strategy of morphogen delivery over long distance by migrating cells.
Highlights
Patterning is defined as the process by which an equipotent field of cells proliferates and organizes into a complex spatial arrangement of distinct cell types in response to positional information [1]
Genetic ablation of one subpopulation leads to a highly dynamic redistribution of the two others. This results in defects in expression of transcription factors and in progenitor cell proliferation, which correlate with the resulting changes in the size and positioning of cortical areas
Given our additional evidence that CR subtypes express specific repertoires of signaling factors, the ablation phenotypes point to a novel early role for CR cells as mediators of cortical patterning and suggest that CR cells are able to signal to progenitor cells
Summary
Patterning is defined as the process by which an equipotent field of cells proliferates and organizes into a complex spatial arrangement of distinct cell types in response to positional information [1]. Patterning mechanisms in early embryos have been studied for many years. These studies have led to the identification of signaling centers and their secreted molecules, some of which mediate their function in a dosedependent manner, such as Fgfs, Bmps, Shh, RA, or Wnts, as well as their antagonists. Morphogens appear to affect patterning (growth and cell fate) over long distances. A major effort has been directed towards understanding how signaling information travels from the source through the surrounding tissues in both vertebrates and Drosophila [6,7], how this leads to graded expression of transcription factors and coordinates growth and cell fate over long distance is still an unresolved issue
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