Notch signaling acts before cell division to promote asymmetric cleavage and cell fate of neural precursor cells

Krishna Moorthi Bhat

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Asymmetric cell divisions in the central nervous system generate neurons of diverse fates. In Drosophila melanogaster, the protein Numb localizes asymmetrically to dividing neural precursor cells such that only one daughter cell inherits Numb. Numb inhibits Notch signaling in this daughter cell, resulting in a different cell fate from the Notch-induced fate in the other-Numb-negative-daughter cell. Precursor cells undergo asymmetric cytokinesis generating daughter cells of different sizes. I found that inactivation of Notch in fly embryonic neural precursor cells disrupted the asymmetric positioning of the cleavage furrow and produced daughter cells of the same size and fate. Moreover, inactivation of Notch at different times altered the degree of asymmetric Numb localization, such that earlier inactivation of Notch caused symmetric distribution of Numb and later inactivation produced incomplete asymmetric localization of Numb. The extent of asymmetrically localized Numb positively correlated with the degree of asymmetric cytokinesis and the size disparity in daughter cells. Loss of Numb or expression of constitutively active Notch led to premature specification of the precursor cells into the fate of one of the daughter cells. Thus, in addition to its role in the specification of daughter cell fate after division, Notch controls Numb localization in the precursor cells to determine the size and fate of daughter cells. Numb also inhibits Notch signaling in precursor cells to prevent Notch-induced differentiation of the precursor cell, forming an autoregulatory loop.

Original languageEnglish (US)
Pages (from-to)ra101
JournalScience Signaling
Volume7
Issue number348
DOIs
StatePublished - Oct 21 2014

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Cell Division
Cells
Specifications
Drosophila Proteins
Neurology
Neurons
Cytokinesis
Cell Size
Asymmetric Cell Division
Drosophila melanogaster
Diptera
Cell Differentiation
Central Nervous System

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Notch signaling acts before cell division to promote asymmetric cleavage and cell fate of neural precursor cells. / Bhat, Krishna Moorthi.

In: Science Signaling, Vol. 7, No. 348, 21.10.2014, p. ra101.

Research output: Contribution to journalArticle

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