ABHD4-dependent developmental anoikis safeguards the embryonic brain

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.

The exact sample size (n) for each experimental group/condition, given as a discrete number and unit of measurement A statement on whether measurements were taken from distinct samples or whether the same sample was measured repeatedly The statistical test(s) used AND whether they are one-or two-sided Only common tests should be described solely by name; describe more complex techniques in the Methods section.
A description of all covariates tested A description of any assumptions or corrections, such as tests of normality and adjustment for multiple comparisons A full description of the statistical parameters including central tendency (e.g. means) or other basic estimates (e.g. regression coefficient) AND variation (e.g. standard deviation) or associated estimates of uncertainty (e.g. confidence intervals) For null hypothesis testing, the test statistic (e.g. F, t, r) with confidence intervals, effect sizes, degrees of freedom and P value noted Give P values as exact values whenever suitable.

For Bayesian analysis, information on the choice of priors and Markov chain Monte Carlo settings
For hierarchical and complex designs, identification of the appropriate level for tests and full reporting of outcomes Estimates of effect sizes (e.g. Cohen's d, Pearson's r), indicating how they were calculated Our web collection on statistics for biologists contains articles on many of the points above.

Software and code
Policy information about availability of computer code Data collection

Data analysis
For manuscripts utilizing custom algorithms or software that are central to the research but not yet described in published literature, software must be made available to editors/reviewers. We strongly encourage code deposition in a community repository (e.g. GitHub). See the Nature Research guidelines for submitting code & software for further information.

István Katona
Jul 27, 2020 In situ and immunofluorescence images: Eclipse 80i upright microscope equipped with a DS-Fi1 CCD camera (Nikon), A1R confocal laserscanning system built on a Ti-E inverted microscope and operated by NIS-Elements AR software 4.50.00 (Nikon). STORM superresolution microscopy: CFI Apo TIRF 100× objective (1.49 NA) on a Ti-E inverted microscope equipped with an N-STORM system, a C2 confocal scan head (Nikon), and an iXon Ultra 897 EMCCD camera (Andor). The system was operated by NIS-Elements AR software version 4.40.00 (Nikon). Western blots: PowerPac HC High-Current Power Supply (Bio-Rad). Ethanol serum level determination: Synchron Systems Ethanol assay kit (Beckman Coulter). Data Policy information about availability of data All manuscripts must include a data availability statement. This statement should provide the following information, where applicable: -Accession codes, unique identifiers, or web links for publicly available datasets -A list of figures that have associated raw data -A description of any restrictions on data availability Field-specific reporting Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences
For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf
Sample size was predetermined based on literature data using the same well established experimental approaches in identical animal models in our laboratory (Cserép et al., Science 367, 528-537 (2020)).
Samples were only excluded from the data analysis when electroporation was unsuccessful.
We confirm that all experiments in this study were replicated successfully at least three times in three different mice or in three independent cell cultures. The same experimental protocol was followed by identical steps of data analysis. Source Data contains exact number of samples and animals used in this study.
All animals and cell culture wells were selected randomly.
The experimenter was always blind to group allocation such as mouse genotype or treatment type. In some cases of electroporation experiments the post hoc analysis were not possible in a completely blinded manner to the striking biological differences between the genotypes (e.g. lack of cell migration).