Long-chain acyl-CoA synthetase(ACSL)plays an essential role in lipid biosynthesis and fatty acid degradation.It converts long-chain fatty acids to acyl-CoAs,the activated substrates essential in lipid metabolism and cell signaling.ACSL4 is highly expressed in the hippocampus,a structure critical for learning and memory.Mutations in ACSL4 are associated with non-syndromic X-linked mental retardation(MRX).However,the neural functions of ACSL4 and how it is involved in the mental retardation remain poorly understood.We report here that dAcsl,the Drosophila ortholog of ACSL4 and ACSL3,exhibits developmental defects of Mushroom body(MB),which is the center of olfactory learning and memory in Drosophila.Loss of dAcsl severely disrupts the development of MB and extends the period of larval developmental stages.dAcsl is required for the normal development of all three types of MB neurons,including γ,α/β and α/β.In addition,dAcsl is required for maintaining the proliferation activity and stemness of MB neuroblasts in a cell-autonomous manner.Thus,our results reveal that dAcsl regulates neuronal morphogenesis in the brain and is required for the proliferation and self-renewing of MB neuroblasts.As Drosophila dAcsl and human ACSL4 are functionally conserved,our findings provide novel insights into the pathogenesis of ACSL4-related mental retardation and putative targets for intervening the pathogenesis.