Non-canonical forms of cannabinoid signaling

One of the major endocannabinoid molecules is anandamide. In this research project we aim to characterize its non-canonical synthesis enzymes, Abhd4 and Gde1, and to describe their diverse physiological functions in the brain.

We published our results on Abhd4 in the prestigious Nature Communications journal.

ABHD4 is expressed in radial glia progenitor cells and triggers apoptosis upon abnormal delamination of these cells thereby preventing pathological developmental processes.

We termed this newly identified safeguarding mechanism developmental anoikis. This process is conceptually analogous to anoikis, a detachment-induced form of apoptosis that is the central protective mechanism against pathological forms of epithelial-mesenchymal transition.

Importantly, the rapid downregulation of ABHD4 was observed following neuronal cell fate commitment under normal conditions indicating that the delaminated daughter neuroblasts escape from anoikis by silencing ABHD4-expression.

Maternal alcohol exposure often results in microcephaly due to the loss of radial glia progenitor cells. To test the relevance of ABHD4 in cell death induced by teratogenic insults, our laboratory also demonstrated the clinical importance of ABHD4-induced cell death in two mouse models of fetal alcohol syndrome.

 

 

 

 

 

 

 

 

 

 

 

 

 

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