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 journalArticle

10 Citations (Scopus)

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

Fingerprint

Ganglia
Stem Cells
Asymmetric Cell Division
Ubiquitin-Protein Ligases
Endocytosis
Transcription Factors
Up-Regulation
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Neuralized mediates asymmetric division of neural precursors by two distinct and sequential events : Promoting asymmetric localization of Numb and enhancing activation of Notch-signaling. / Bhat, Krishna Moorthi; Gaziova, Ivana; Katipalla, Sumana.

In: Developmental Biology, Vol. 351, No. 1, 01.03.2011, p. 186-198.

Research output: Contribution to journalArticle

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