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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Rep 2016 ; 14 (5): 991-9 Nephropedia Template TP
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Inborn Errors of Long Chain Fatty Acid ?-Oxidation Link Neural Stem Cell Self-Renewal to Autism #MMPMID26832401
Xie Z; Jones A; Deeney JT; Hur SK; Bankaitis VA
Cell Rep 2016[Feb]; 14 (5): 991-9 PMID26832401show ga
Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid ?-oxidation (FAO) clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in activity of TMLHE (an autism-risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in mammalian embryonic brain, and suggest NSC self-renewal as a cellular mechanism underlying the association between IEMs and autism.