Drosophila homolog of the intellectual disability-related long-chain acyl-CoA synthetase 4 is required for neuroblast proliferation

Mingyue Jia^{a, b, #},
Danqing Meng^{a, b, #},
Mo Chen^{a, b, #},
Tingting Li^{a, b},
Yong Q. Zhang^{a, b
, ,},
Aiyu Yao^{a
, ,}

a.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
b.
University of Chinese Academy of Sciences, Beijing, 100049, China

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Corresponding author: E-mail address: yqzhang@genetics.ac.cn (Yong Q. Zhang); E-mail address: ayyao@genetics.ac.cn (Aiyu Yao)

These authors contributed equally to this work.

摘要

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Abstract: Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic X-linked intellectual disability (ID). However, the neural functions of ACSL4 and how loss of ACSL4 leads to ID remain largely unexplored. We report here that mutations in Acsl, the Drosophila ortholog of human ACSL3 and ACSL4, result in developmental defects of the mushroom body (MB), the center of olfactory learning and memory. Specifically, Acsl mutants show fewer MB neuroblasts (Nbs) due to reduced proliferation activity and premature differentiation. Consistently, these surviving Nbs show reduced expression of cyclin E, a key regulator of the G1- to S-phase cell cycle transition, and nuclear mislocalization of the transcriptional factor Prospero, which is known to repress self-renewal genes and activate differentiating genes. Furthermore, RNA-seq analysis reveals downregulated Nb- and cell-cycle-related genes and upregulated neuronal differentiation genes in Acsl mutant Nbs. As Drosophila Acsl and human ACSL4 are functionally conserved, our findings provide novel insights into a critical and previously unappreciated role of Acsl in neurogenesis and the pathogenesis of ACSL4-related ID.
- ACSL4 /
- Mushroom body /
- Neuroblast /
- Neural stem cell /
- Premature differentiation
These authors contributed equally to this work.
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doi: 10.1016/j.jgg.2018.10.006

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Drosophila homolog of the intellectual disability-related long-chain acyl-CoA synthetase 4 is required for neuroblast proliferation

Corresponding author: E-mail address: yqzhang@genetics.ac.cn (Yong Q. Zhang); E-mail address: ayyao@genetics.ac.cn (Aiyu Yao)

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doi: 10.1016/j.jgg.2018.10.006

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Drosophila homolog of the intellectual disability-related long-chain acyl-CoA synthetase 4 is required for neuroblast proliferation

Corresponding author: E-mail address: yqzhang@genetics.ac.cn (Yong Q. Zhang); E-mail address: ayyao@genetics.ac.cn (Aiyu Yao)

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