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Publication : Dmrt factors determine the positional information of cerebral cortical progenitors via differential suppression of homeobox genes.

First Author  Konno D Year  2019
Journal  Development Volume  146
Issue  15 PubMed ID  31371378
Mgi Jnum  J:284155 Mgi Id  MGI:6389858
Doi  10.1242/dev.174243 Citation  Konno D, et al. (2019) Dmrt factors determine the positional information of cerebral cortical progenitors via differential suppression of homeobox genes. Development 146(15):dev174243
abstractText  The spatiotemporal identity of neural progenitors and the regional control of neurogenesis are essential for the development of cerebral cortical architecture. Here, we report that mammalian DM domain factors (Dmrt) determine the identity of cerebral cortical progenitors. Among the Dmrt family genes expressed in the developing dorsal telencephalon, Dmrt3 and Dmrta2 show a medial(high)/lateral(low) expression gradient. Their simultaneous loss confers a ventral identity to dorsal progenitors, resulting in the ectopic expression of Gsx2 and massive production of GABAergic olfactory bulb interneurons in the dorsal telencephalon. Furthermore, double-mutant progenitors in the medial region exhibit upregulated Pax6 and more lateral characteristics. These ventral and lateral shifts in progenitor identity depend on Dmrt gene dosage. We also found that Dmrt factors bind to Gsx2 and Pax6 enhancers to suppress their expression. Our findings thus reveal that the graded expression of Dmrt factors provide positional information for progenitors by differentially repressing downstream genes in the developing cerebral cortex.
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