ABHD4-dependent developmental anoikis protects the prenatal brain from pathological insults

In light of the astronomical number of cell divisions taking place in restricted neurogenic niches, brain malformations caused by ectopic proliferation of misplaced progenitor cells are surprisingly rare. Here, we show that a process we term developmental anoikis distinguishes the abnormal detachmen...

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Published inbioRxiv
Main Authors Laszlo, Zsofia, Lele, Zsolt, Zoldi, Miklos, Miczan, Vivien, Mogor, Fruzsina, Simon, Gabriel M, Mackie, Ken, Kacskovics, Imre, Cravatt, Benjamin F, Katona, Istvan
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 18.12.2019
Subjects
Anoikis
Apoptosis
Brain injury
Cell death
Cell proliferation
Embryos
Neocortex
Neuroblasts
Neuroimaging
Progenitor cells
Stem cells
Teratogenicity
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Summary:In light of the astronomical number of cell divisions taking place in restricted neurogenic niches, brain malformations caused by ectopic proliferation of misplaced progenitor cells are surprisingly rare. Here, we show that a process we term developmental anoikis distinguishes the abnormal detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. By using in vivo gain-of-function, loss-of-function, and rescue manipulations together with correlated confocal and super-resolution imaging, we identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of abnormally 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.
DOI:10.1101/2019.12.17.879551