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XB-ART-51355
Development October 1, 2015; 142 (19): 3416-28.

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus.

Thélie A , Desiderio S , Hanotel J , Quigley I , Van Driessche B , Rodari A , Borromeo MD , Kricha S , Lahaye F , Croce J , Cerda-Moya G , Ordoño Fernandez J , Bolle B , Lewis KE , Sander M , Pierani A , Schubert M , Johnson JE , Kintner CR , Pieler T , Van Lint C , Henningfeld KA , Bellefroid EJ , Van Campenhout C .


Abstract
V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genome-wide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages.

PubMed ID: 26443638
PMC ID: PMC4631751
Article link: Development
Grant support: [+]
Genes referenced: ccndx cdknx cyp26a1 dbx1 dbx2 egr2 ehmt2 en1 evx1 gad1.1 grpr irx3 krt12.4 lhx1 lhx3 lhx5 mafb mcidas mnx1 neurog2 nkx6-1 nkx6-2 nog nxph2 otx2 pax2 pax3 pax6 pax7 prdm12 prdm13 ptf1a shh slc32a1 slc6a5 sox3 tubb2b vsx1
Morpholinos: dbx1 MO1 nkx6-1 MO3 nkx6-2 MO1 pax6 MO1 prdm12 MO2 prdm12 MO3

OMIMs: NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IA; HSAN1A
GEO Series:
   GSE64551: Xenbase,  NCBI


Article Images: [+] show captions
References:
Alvarez, 2005, Pubmed [+]


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