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A new role for Notch in the control of polarity and asymmetric cell division of developing T cells
- Source :
- Journal of cell science. 133(5)
- Publication Year :
- 2019
-
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.
- Subjects :
- Cell signaling
Cell type
Receptors, CXCR4
Cellular differentiation
T cell
T-Lymphocytes
Beta selection
Notch signaling pathway
Nerve Tissue Proteins
Cell Communication
Biology
Cell fate determination
CXCR4
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Cell polarity
medicine
Asymmetric cell division
Animals
Humans
Receptor, Notch1
Cells, Cultured
030304 developmental biology
Cell Proliferation
0303 health sciences
Cell Death
Asymmetric Cell Division
Cell Polarity
Membrane Proteins
Cell Differentiation
Cell Biology
Hematopoietic Stem Cells
Cell biology
Mice, Inbred C57BL
Signalling
medicine.anatomical_structure
030220 oncology & carcinogenesis
NUMB
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 14779137
- Volume :
- 133
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of cell science
- Accession number :
- edsair.doi.dedup.....4f6473f25ae4be75600ff93117cf4da3