High impact information on Numbl

• This resulted in severe damage to brain lateral ventricle integrity and identified roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival [1].
• 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 [2].
• Progenitor cell maintenance requires numb and numblike during mouse neurogenesis [2].
• We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates [2].
• Taken together, our data provide evidence for previously unidentified functions of Numb and Numblike in sensory axon arborization by regulating Notch1 via the endocytic-lysosomal pathways [3].

Biological context of Numbl

• Because progenitor cells can proliferate without Numb and Numbl before neurogenesis, we propose that Numb-mediated asymmetric cell divisions, which diversify many cell fates in Drosophila melanogaster, represent a general mechanism in mammals for stem cells to balance self-renewal and differentiation [4].
• Numb and Numblike control cell number during vertebrate neurogenesis [5].
• Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis [6].
• We searched for the TCF/LEF-binding site within the promoter region of NUMB and NUMBL genes [7].

Anatomical context of Numbl

• Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis [4].
• As occurs during early neurogenesis, the loss of Numb and Numbl causes premature progenitor-cell depletion and, consequently, a highly specific malformation of the neocortex and hippocampus [4].
• Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization [3].
• Here we demonstrate that conditional mouse mutants with deletion of numb and numblike in developing sensory ganglia show a severe reduction in axonal arborization in afferent fibers, but no deficit in neurogenesis [3].
• Using Emx1(IREScre) to induce more restricted inactivation of Numb in the dorsal forebrain of numblike null mice beginning at E9.5, we have generated viable double mutants that displayed striking brain defects [6].

Other interactions of Numbl

• 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 [8].

References