DIFFERENTIAL EXPRESSION OF MAMMALIAN NUMB, NUMBLIKE AND NOTCH1 SUGGESTS DISTINCT ROLES DURING MOUSE CORTICAL NEUROGENESIS

During Drosophila neurogenesis, asymmetric cell divisions are achieved by differential segregation of Numb (d-Numb) into one of the daughter cells to cause a bias in the Notch mediated cell-cell interaction, We have isolated a second mammalian gene with significant sequence simil arity to d-numb, mouse numblike. When expressed in dividing neural pre cursors in Drosophila, Numblike is symmetrically distributed in the cy toplasm, unlike endogenous d-Numb or expressed mouse Numb (m-Numb), bo th of which are asymmetrically localized to one half of the cell membr ane, In d-numb loss-of-function mutant embryos, expression of Numblike allows both daughter cells of a neural precursor to adopt the fate of the cell that normally inherits d-Numb, In mice, numblike mRNA is pre ferentially expressed in adult and embryonic nervous system. In the de veloping neocortex, Numblike is expressed in postmitotic neurons in th e cortical plate, but not in progenitors within the ventricular zone w here m-Numb and Notchl are expressed, We have also found that, in divi ding cortical progenitors, Notchl is distributed around the entire mem brane, unlike m-Numb which is asymmetrically localized to the apical m embrane, We propose that an interplay between cell-intrinsic mechanism s (executed by m-numb and numblike) and cell-extrinsic mechanisms (med iated by Notch1) may be involved in both progenitor cell proliferation and neuronal differentiation during mammalian cortical neurogenesis.