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Sp9 Regulates Medial Ganglionic Eminence-Derived Cortical Interneuron Development

Author:
Liu, Zhidong  Zhang, Zhuangzhi  Lindtner, Susan  Li, Zhenmeiyu  Xu, Zhejun  Wei, Song  Liang, Qifei  Wen, Yan  Tao, Guangxu  You, Yan  Chen, Bin  Wang, Yanling  Rubenstein, John L.  Yang, Zhengang  


Journal:
CEREBRAL CORTEX


Issue Date:
2019


Abstract(summary):

Immature neurons generated by the subpallial MGE tangentially migrate to the cortex where they become parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons. Here, we show that the Sp9 transcription factor controls the development of MGE-derived cortical interneurons. SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons. Sp9 null and conditional mutant mice have approximately 50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. RNA-Seq and SP9 ChIP-Seq reveal that SP9 regulates MGE-derived cortical interneuron development through controlling the expression of key transcription factors Arx, Lhx6, Lhx8, Nkx2-1, and Zeb2 involved in interneuron development, as well as genes implicated in regulating interneuron migration Ackr3, Epha3, and St18. Thus, Sp9 has a central transcriptional role in MGE-derived cortical interneuron development.


Page:
2653---2667


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