Results

The Genetics of numb In an attempt to identify genes affecting neuronal development, we have examined a collection of single P eiement-induced lethal lines (Cooley et al., 1988a, 1988b) for mutants with abnormal peripheral nervous systems. numb was identified as a mutation that removes the majority of sensory neurons. This mutation is most likely caused by the transposon, because the P element is inserted at cytological position 308 (data not shown), and a chromosome having a deletion of the 3OA-30C region fails to complement this numb mutation (numb’). Moreover, reversion of the mutant phenotype was associated with the excision of this P element (12 out of 12 cases), confirming that the insertion is responsible for the phenotype of numb mutants (see details in Experimental Procedures). in addition to numb’, we generated two diepoxybutane (DEB)-induced alleles. All three alleles appear to be null, because the phenotypes of homozygous mutant embryos are indistinguishable from those of the same alleles carried over the deletion, and because embryos homozygous for the deletion produce a neuronai phenotype in the periphery similar to that of homozygous numb mutant embryos. Thus the numb mutant phenotype described below is a loss-of-function phenotype and is characteristic of each of the three null alleles. numb Mutant Embryos Lack Most of the Neurons in the Periphery

The number of peripheral neurons is severely reduced in homozygous numb embryos. This is evident in 12-14 hr embryos stained with a neuronal-specific marker, antihorseradish peroxidase antibody (anti-HRP)(Jan and Jan, 1982)(Figure lB), as well as in embryos stained with other antibodies that recognize all sensory neurons (monoclonal antibodies [MAbs] 21A4 and 44Cll). Compared with