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XB-ART-48401
Dev Biol February 15, 2014; 386 (2): 340-57.

The Prdm13 histone methyltransferase encoding gene is a Ptf1a-Rbpj downstream target that suppresses glutamatergic and promotes GABAergic neuronal fate in the dorsal neural tube.

Hanotel J , Bessodes N , Thélie A , Hedderich M , Parain K , Van Driessche B , Brandão Kde O , Kricha S , Jorgensen MC , Grapin-Botton A , Serup P , Van Lint C , Perron M , Pieler T , Henningfeld KA , Bellefroid EJ .


Abstract
The basic helix-loop-helix (bHLH) transcriptional activator Ptf1a determines inhibitory GABAergic over excitatory glutamatergic neuronal cell fate in progenitors of the vertebrate dorsal spinal cord, cerebellum and retina. In an in situ hybridization expression survey of PR domain containing genes encoding putative chromatin-remodeling zinc finger transcription factors in Xenopus embryos, we identified Prdm13 as a histone methyltransferase belonging to the Ptf1a synexpression group. Gain and loss of Ptf1a function analyses in both frog and mice indicates that Prdm13 is positively regulated by Ptf1a and likely constitutes a direct transcriptional target. We also showed that this regulation requires the formation of the Ptf1a-Rbp-j complex. Prdm13 knockdown in Xenopus embryos and in Ptf1a overexpressing ectodermal explants lead to an upregulation of Tlx3/Hox11L2, which specifies a glutamatergic lineage and a reduction of the GABAergic neuronal marker Pax2. It also leads to an upregulation of Prdm13 transcription, suggesting an autonegative regulation. Conversely, in animal caps, Prdm13 blocks the ability of the bHLH factor Neurog2 to activate Tlx3. Additional gain of function experiments in the chick neural tube confirm that Prdm13 suppresses Tlx3(+)/glutamatergic and induces Pax2(+)/GABAergic neuronal fate. Thus, Prdm13 is a novel crucial component of the Ptf1a regulatory pathway that, by modulating the transcriptional activity of bHLH factors such as Neurog2, controls the balance between GABAergic and glutamatergic neuronal fate in the dorsal and caudal part of the vertebrate neural tube.

PubMed ID: 24370451
Article link: Dev Biol

Genes referenced: ascl1 dbx1 egr2 en2 gad1.1 h4c4 lbx1 lmx1b.1 lmx1b.2 mafb myt1 neurod1 neurog2 pax2 prdm13 prdm16 prdm8 ptf1a rbpj slc17a7 sox3 tbx2 tlx3 trhd tubb2b
Morpholinos: neurog2 MO2 prdm13 MO1 ptf1a MO3


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