Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production.

Autor: Turrero García M; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Baizabal JM; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Tran DN; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Peixoto R; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Wang W; Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Xie Y; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Adam MA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., English LA; Summer Honors Undergraduate Research Program, Harvard Medical School, Boston, MA 02115, USA., Reid CM; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Brito SI; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Booker MA; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Tolstorukov MY; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02115, USA., Harwell CC; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA corey_harwell@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Development (Cambridge, England) [Development] 2020 Nov 16; Vol. 147 (22). Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1242/dev.187526
Abstrakt: The mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from the dorsal telencephalon, whereas inhibitory interneurons are generated in its ventral portion. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear whether PRDM16 plays a similar role in neurogenesis in both dorsal and ventral progenitor lineages and, if so, whether it regulates common or unique networks of genes. Here, we show that Prdm16 expression in mouse medial ganglionic eminence (MGE) progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of forebrain GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. PRDM16 regulates convergent developmental gene expression programs in the cortex and MGE, which utilize both common and region-specific sets of genes to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.
Competing Interests: Competing interestsThe authors declare no competing or financial interests.
(© 2020. Published by The Company of Biologists Ltd.)
Databáze: MEDLINE