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J Cell Sci. 2019 Oct 24;133(5). pii: jcs235358. doi: 10.1242/jcs.235358.

A new role for Notch in the control of polarity and asymmetric cell division of developing T cells.

Author information

1
Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia mcharnley@swin.edu.au sarah.russell@petermac.org.
2
Biointerface Engineering, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
3
Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Parkville, Victoria 3000, Australia.
4
Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
5
Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia.
6
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria 3010, Australia.

Abstract

A fundamental question in biology is how single cells can reliably produce progeny of different cell types. Notch signalling frequently facilitates fate determination. Asymmetric cell division (ACD) often controls segregation of Notch signalling by imposing unequal inheritance of regulators of Notch. Here, we assessed the functional relationship between Notch and ACD in mouse T cell development. To attain immunological specificity, developing T cells must pass through a pivotal stage termed β-selection, which involves Notch signalling and ACD. We assessed functional interactions between Notch1 and ACD during β-selection through direct presentation of Notch ligands, DL1 and DL4, and pharmacological inhibition of Notch signalling. Contrary to prevailing models, we demonstrate that Notch signalling controls the distribution of Notch1 itself and cell fate determinants, α-adaptin and Numb. Furthermore, Notch and CXCR4 signalling cooperated to drive polarity during division. Thus, Notch signalling directly orchestrates ACD, and Notch1 is differentially inherited by sibling cells.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Asymmetric cell division; CXCR4; DN3; Developing T cell; Notch; β-selection

PMID:
31578237
DOI:
10.1242/jcs.235358

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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