Numb Suppresses Notch-Dependent Activation of during Lateral Inhibition in the Embryonic Nervous System.

The role of in regulating Notch signaling and neurogenesis has been extensively studied, with a particular focus on its effects on the peripheral nervous system (PNS). Previous studies based on a single loss-of-function allele of , , showed an antineurogenic effect on the peripheral nervous system (PNS), which revealed that the wild-type suppresses Notch signaling. In the current study, we examined whether this phenotype is consistently observed in loss-of-function mutations of Two more alleles, and , were shown to have an antineurogenic phenotype in the PNS. We also found that introducing a wild-type genomic fragment into homozygotes rescued their antineurogenic phenotype. These results demonstrated that loss-of-function mutations of universally induce this phenotype. Many components of Notch signaling are encoded by maternal effect genes, but no maternal effect of was observed in this study. The antineurogenic phenotype of was found to be dependent on the (()), a downstream gene of Notch signaling. We found that the combination of () homozygous and homozygous suppressed the neurogenic phenotype of the embryonic central nervous system (CNS) associated with the () mutation. In the allele, genes encoding basic helix-loop-helix proteins, such as , , , and m8, remain. Thus, in the allele, derepression of Notch activity by mutation can rescue the neurogenic phenotype by increasing the expression of the remaining genes in the complex. We also uncovered a role for in regulating neuronal projections. Our results further support an important role for in the suppression of Notch signaling during embryonic nervous system development.