During neurogenesis of the mammalian neocortex, neural progenitor cells div
ide to generate daughter cells that either become neurons or remain as prog
enitor cells. The mouse numb (m-numb) gene encodes a membrane-associated pr
otein that is asymmetrically localized to the apical cell membrane of divid
ing cortical progenitor cells and may be segregated to only the apical daug
hter cell that has been suggested to remain as a progenitor cell. To examin
e m-numb function during neural development, we generated a loss-of-functio
n mutant allele of m-numb. Mice homozygous for this mutation exhibit severe
defects in cranial neural tube closure and precocious neuron production in
the forebrain and die around embryonic day 11.5 (E11.5). These findings su
ggest that m-numb is an essential gene that plays a role in promoting proge
nitor cell fate during cortical neurogenesis.