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 similarity to d-numb, mouse numblike. When expressed in dividing neural precursors in Drosophila, Numblike is symmetrically distributed in the cytoplasm, unlike endogenous d-Numb or expressed mouse Numb (m-Numb), both of which are asymmetrically localized to one half of the cell membrane. 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 preferentially expressed in adult and embryonic nervous system. In the developing neocortex, Numblike is expressed in postmitotic neurons in the cortical plate, but not in progenitors within the ventricular zone where m-Numb and Notch1 are expressed. We have also found that, in dividing cortical progenitors, Notch1 is distributed around the entire membrane, unlike m-Numb which is asymmetrically localized to the apical membrane. We propose that an interplay between cell-intrinsic mechanisms (executed by m-numb and numblike) and cell-extrinsic mechanisms (mediated by Notch1) may be involved in both progenitor cell proliferation and neuronal differentiation during mammalian cortical neurogenesis.
Zhong
W
W
Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco, 94143, USA.
Jiang
M M
MM
Weinmaster
G
G
Jan
L Y
LY
Jan
Y N
YN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007605:Juvenile Hormones / Q000235:genetics; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D009420:Nervous System / Q000737:chemistry / Q000196:embryology; D009474:Neurons / Q000737:chemistry; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000737:chemistry; D014157:Transcription Factors
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007605:Juvenile Hormones; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; C106293:Numb protein, mouse; C106292:Numbl protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C060606:numb protein, Drosophila