Notch signaling is required for the maintenance of enteric neural crest progenitors
2008
Notch signaling is involved in neurogenesis, including that of the
peripheral nervous system as derived from neural crest cells (NCCs). However,
it remains unclear which step is regulated by this signaling. To address this
question, we took advantage of the Cre-loxP system to specifically eliminate
the protein O -fucosyltransferase 1 ( Pofut1 ) gene, which is a
core component of Notch signaling, in NCCs. NCC-specific
Pofut1 -knockout mice died within 1 day of birth, accompanied by a
defect of enteric nervous system (ENS) development. These embryos showed a
reduction in enteric neural crest cells (ENCCs) resulting from premature
neurogenesis. We found that Sox10 expression, which is normally maintained in
ENCC progenitors, was decreased in Pofut1 -null ENCCs. By contrast,
the number of ENCCs that expressed Mash1, a potent repressor of Sox10, was
increased in the Pofut1 -null mouse. Given that Mash1 is suppressed
via the Notch signaling pathway, we propose a model in which ENCCs have a
cell-autonomous differentiating program for neurons as reflected in the
expression of Mash1, and in which Notch signaling is required for the
maintenance of ENS progenitors by attenuating this cell-autonomous program via
the suppression of Mash1.
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