Journal
CEREBRAL CORTEX
Volume 29, Issue 11, Pages 4831-4849Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhz018
Keywords
Ascl1; Pax6; Dlx1; Dlx2; Gsx2; interneuron; olfactory bulb; Sp8; Sp9
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Funding
- National Key Research and Development Program of China [2018YFA0108000]
- National Natural Science Foundation of China [NSFC 31820103006, 31630032, 31425011, 31429002]
- National Institute of Mental Health [R01MH094589, R37MH049428]
- National Institute of Neurological Disorders and Stroke [R01NS089777]
- [NSFC 31700889]
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Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2(+) and ASCL1(+) neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2(F/-) mice), GSX2(+) and ASCL1(+) neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.
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