Neuralized mediates asymmetric division of neural precursors by two distinct and sequential events: Promoting asymmetric localization of Numb and enhancing activation of Notch-signaling

Krishna Moorthi Bhat, Ivana Gaziova, Sumana Katipalla

    Research output: Contribution to journalArticlepeer-review

    15 Scopus citations

    Abstract

    In the CNS, the evolutionarily conserved Notch pathway regulates asymmetric cell fate specification to daughters of ganglion mother cells (GMCs). The E3 Ubiquitin ligase protein Neuralized (Neur) is thought to activate Notch-signaling by the endocytosis of Delta and the Delta-bound extracellular domain of Notch. The intracellular Notch then initiates Notch-signaling. Numb blocks N-signaling in one of the two daughters of a GMC, allowing that cell to adopt a different identity. Numb is asymmetrically localized in a GMC and is segregated to only one of the two daughter cells. In the typical GMC-1→RP2/sib lineage, we found that loss of Neur activity causes symmetric division of GMC-1 into two RP2s. We further found that Neur asymmetrically localizes in a late GMC-1 to the Numb domain and Neur mediates asymmetric division via two distinct, sequential mechanisms: by promoting the asymmetric localization of Numb in a GMC-1 via down-regulation of the transcription factor Pdm1, followed by enhancing the Notch-signaling via trans-potentiation of Notch in a cell committed to become a sib. In neur mutants the GMC-1 identity is not altered but Numb is non-asymmetrically localized due to an up-regulation of Pdm1. Thus, both its daughters inherit Numb, which prevents Notch from specifying a sib identity. Neur also enhances Notch since in neur; numb double mutants, both sibling cells often adopt a mixed fate as opposed to an RP2 fate observed in Notch; numb double mutants. Furthermore, over-expression of Neur can induce both cells to adopt a sib fate similar to gain of function Notch. Our results tie Numb and Notch-signaling through a single player, Neur, thus giving us a more complete picture of the events surrounding asymmetric division of precursor cells. We also show that Neur and Numb are interdependent for their asymmetric-localizations.

    Original languageEnglish (US)
    Pages (from-to)186-198
    Number of pages13
    JournalDevelopmental Biology
    Volume351
    Issue number1
    DOIs
    StatePublished - Mar 1 2011

    Keywords

    • Asymmetric division
    • Neural precursor
    • Neuralized
    • Notch
    • Numb

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Neuralized mediates asymmetric division of neural precursors by two distinct and sequential events: Promoting asymmetric localization of Numb and enhancing activation of Notch-signaling'. Together they form a unique fingerprint.

    Cite this