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Caenorhabditis elegans ced-3 Caspase Is Required for Asymmetric Divisions That Generate Cells Programmed To Die

Mishra, N; Wei, H; Conradt, B; (2018) Caenorhabditis elegans ced-3 Caspase Is Required for Asymmetric Divisions That Generate Cells Programmed To Die. Genetics , 210 (3) pp. 983-998. 10.1534/genetics.118.301500.

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Abstract

Caspases have functions other than in apoptosis. Here, we report that Caenorhabditis elegans CED-3 caspase regulates asymmetric cell division. Many of the 131 cells that are “programmed” to die during C. elegans development are the smaller daughter of a neuroblast that divides asymmetrically by size and fate. We have previously shown that CED-3 caspase is activated in such neuroblasts, and that before neuroblast division, a gradient of CED-3 caspase activity is formed in a ced-1 MEGF10 (multiple EGF-like domains 10)-dependent manner. This results in the nonrandom segregation of active CED-3 caspase or “apoptotic potential” into the smaller daughter. We now show that CED-3 caspase is necessary for the ability of neuroblasts to divide asymmetrically by size. In addition, we provide evidence that a pig-1 MELK (maternal embryonic leucine zipper kinase)-dependent reciprocal gradient of “mitotic potential” is formed in the QL.p neuroblast, and that CED-3 caspase antagonizes this mitotic potential. Based on these findings, we propose that CED-3 caspase plays a critical role in the asymmetric division by size and fate of neuroblasts, and that this contributes to the reproducibility and robustness with which the smaller daughter cell is produced and adopts the apoptotic fate. Finally, the function of CED-3 caspase in this context is dependent on its activation through the conserved egl-1 BH3-only, ced-9 Bcl-2, and ced-4 Apaf-1 pathway. In mammals, caspases affect various aspects of stem cell lineages. We speculate that the new nonapoptotic function of C. elegans CED-3 caspase in asymmetric neuroblast division is relevant to the function(s) of mammalian caspases in stem cells.

Type: Article
Title: Caenorhabditis elegans ced-3 Caspase Is Required for Asymmetric Divisions That Generate Cells Programmed To Die
DOI: 10.1534/genetics.118.301500
Publisher version: https://doi.org/10.1534/genetics.118.301500
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Caspase, non-apoptotic function, asymmetric cell division, neuroblasts, C. elegans, pig-1 MELK
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10070499
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