ABHD4-dependent developmental anoikis safeguards the embryonic brain

Zsófia I. László, Zsolt Lele, Miklós Zöldi, Vivien Miczán, Fruzsina Mógor, Gabriel M. Simon, Ken Mackie, Imre Kacskovics, Benjamin F. Cravatt and István Katona ()
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Zsófia I. László: Institute of Experimental Medicine
Zsolt Lele: Institute of Experimental Medicine
Miklós Zöldi: Institute of Experimental Medicine
Vivien Miczán: Institute of Experimental Medicine
Fruzsina Mógor: Institute of Experimental Medicine
Gabriel M. Simon: The Scripps Research Institute
Ken Mackie: Indiana University
Imre Kacskovics: Eötvös Loránd University
Benjamin F. Cravatt: The Scripps Research Institute
István Katona: Institute of Experimental Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract A specialized neurogenic niche along the ventricles accumulates millions of progenitor cells in the developing brain. After mitosis, fate-committed daughter cells delaminate from this germinative zone. Considering the high number of cell divisions and delaminations taking place during embryonic development, brain malformations caused by ectopic proliferation of misplaced progenitor cells are relatively rare. Here, we report that a process we term developmental anoikis distinguishes the pathological detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. We identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of pathologically detached cells. Consequently, rapid ABHD4 downregulation is necessary for delaminated daughter neuroblasts to escape from anoikis. Moreover, ABHD4 is required for fetal alcohol-induced apoptosis, but not for the well-established form of developmentally controlled programmed cell death. These results suggest that ABHD4-mediated developmental anoikis specifically protects the embryonic brain from the consequences of sporadic delamination errors and teratogenic insults.

Date: 2020
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DOI: 10.1038/s41467-020-18175-4

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