Notch signaling is required for the maintenance of enteric neural crest progenitors.
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.
Okamura
Yoshiaki
Y
Department of Genetics, SOKENDAI, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Saga
Yumiko
Y
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology; D017615:Enteric Nervous System / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D005647:Fucosyltransferases / Q000172:deficiency / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009432:Neural Crest / Q000166:cytology* / Q000201:enzymology; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D055757:SOXE Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D008024:Ligands; D051880:Receptors, Notch; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D005647:Fucosyltransferases; C105148:polypeptide fucosyltransferase