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Heterogeneity and clinical potential of boundary cap cells and their derivatives

Authors
  • Gerschenfeld, Gaspard
Publication Date
Jun 04, 2019
Source
HAL-Descartes
Keywords
Language
English
License
Unknown
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Abstract

In addition to glia and neurons, the neural crest gives rise to boundary cap cells (BC) that form transient clusters at the entry/exit points of all cranial and spinal nerves. Fate-mapping experiments have revealed that BC derivatives migrate along nerve roots into the dorsal root ganglia (DRG) and then peripheral nerves to reach the skin. Whereas BC are at the origin of most nerve root Schwann cells (SC) and a subpopulation of DRG sensory neurons (SN), in the skin they give rise to SC, terminal glia and a population of stem-like skin progenitor cells (SKP). Recent experiments using another BC marker Krox20 have revealed that while their derivatives in nerve roots and DRG are similar, those reaching the skin detach from nerves, undergo a “glial to vascular” switch and provide mural cells to the developing vasculature. In my thesis, I have focused my efforts on understanding the mechanisms of this “glial to vascular” switch. I have shown that: (i) Krox20-traced BC derivatives detachment from nerves occurs between E12.5 and E15.5, concomitantly with the extinction of glial and the activation of mural markers; (ii) about a third of adult skin mural cells originate from BC cells; (iii) the expression of several mural markers is detectable at E12.5 in cells closely attached to axons suggesting that their switch of identity occurs well before their detachment (iv) in addition to mural cells, they also give rise to perivascular fibroblast-like cells, a cell population recently described in central nervous system fibrosis. These findings suggest a new development model, in which peripheral glia first acts as a source of mural cells before providing signals to shape blood vessels.

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