1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
2. Howard Hughes Medical Institute and Departments of Physiology and Biochemistry, University of California, San Francisco, California 94143, USA
3. These authors contributed equally to this work

Correspondence to: Weimin Zhong¹ Correspondence and requests for materials should be addressed to W.Z. (e-mail: Email: weimin.zhong@yale.edu).

Abstract

Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types^{1, 2, 3}. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl)^{4, 5, 6}, two highly conserved homologues of Drosophila numb^{7, 8}, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities.