期刊
CEREBRAL CORTEX
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhad281
关键词
DOT1L; Foxg1; GABAergic interneurons; Nkx2; 1; parvalbumin
This study reveals that DOT1L plays a crucial role in the development of inhibitory neurons in the cortex, with its deletion resulting in a decrease in GABAergic interneuron numbers and altered distribution in the cortex.
The cortical plate (CP) is composed of excitatory and inhibitory neurons, the latter of which originate in the ganglionic eminences. From their origin in the ventral telencephalon, maturing postmitotic interneurons migrate during embryonic development over some distance to reach their final destination in the CP. The histone methyltransferase Disruptor of Telomeric Silencing 1-like (DOT1L) is necessary for proper CP development and layer distribution of glutamatergic neurons. However, its specific role on cortical interneuron development has not yet been explored. Here, we demonstrate that DOT1L affects interneuron development in a cell autonomous manner. Deletion of Dot1l in Nkx2.1-expressing interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the CP from postnatal day 0 onwards. We observed an altered proportion of GABAergic interneurons in the cortex, with a significant decrease in parvalbumin-expressing interneurons. Moreover, a decreased number of mitotic cells at the embryonic day E14.5 was observed upon Dot1l deletion. Altogether, our results indicate that reduced numbers of cortical interneurons upon DOT1L deletion result from premature cell cycle exit, but effects on postmitotic differentiation, maturation, and migration are likely at play as well.
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