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Semenkovich and collaborators publish in Proceedings of the National Academy of Sciences

Clay F. Semenkovich, MD
Clay F. Semenkovich, MD

On January 11, Clay F. Semenkovich, MD and collaborators had their research titled, “FASN-dependent de novo lipogenesis is required for brain development,” published in the “Proceedings of the National Academy of Sciences.” 

De novo lipogenesis is a metabolic pathway, which is essential to governing progenitor function through supplying energy and providing molecular building blocks that generate cells. De novo lipogenesis is defined as the “conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN).” Although its role in brain development has remained unclear, Semenkovich and collaborators were able to identify a link between progenitor-cell polarity and lipid metabolism.  

By taking the dual approach of using mouse genetics and human forebrain organoids in their research, they discovered an important role that FASN-dependent de novo lipogenesis plays in the brain development of both mice and humans. Measuring FASN levels in the cortex at various developmental time points using immunofluorescence, confirmed the efficiency of genetic FASN deletion — revealing that “emx1Cre-mediated deletion of FASN caused severe disorganization of cortical layers.” When comparing the data, they found that microcephaly was indeed a result of FASN genetic deletion in mouse embryonic telencephalon.  

Furthermore, presenting the conclusion that “genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell–derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids.” These findings emphasize the importance of FASN-dependent de novo lipogenesis, and that “regulation of cellular metabolism in proliferating progenitor cells and their neuronal progeny is critical for brain development and function.” 

FASN-dependent de novo lipogenesis is required for brain development