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Background  Functioning of the adult nervous system depends on the establishment of neural circuits during embryogenesis. In vertebrates, neurons that make up motor circuits form in distinct domains along the dorsoventral axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing fates of adjacent domains. The  prdm12  TF is required for the expression of  eng1b  and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear.    Methods  We used CRISPR/Cas9 to generate the first germline mutants for  prdm12  and employed this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study  prdm12b  function in zebrafish. We also generated germline mutants for  bhlhe22  and  nkx6.1  to examine how these TFs act with  prdm12b  to control p1 formation.    Results  We find that  prdm12b  mutants lack  eng1b  expression in the p1 domain and also possess an abnormal touch-evoked escape response. Using luciferase reporter assays, we demonstrate that Prdm12b acts as a transcriptional repressor. We also show that the Bhlhe22 TF binds via the Prdm12b zinc finger domain to form a complex. However,  bhlhe22  mutants display normal  eng1b  expression in the p1 domain. While  prdm12  has been proposed to promote p1 fates by repressing expression of the  nkx6.1  TF, we do not observe an expansion of the  nkx6.1  domain upon loss of  prdm12b  function, nor is  eng1b  expression restored upon simultaneous loss of  prdm12b  and  nkx6.1.Conclusions  We conclude that  prdm12b  germline mutations produce a phenotype that is indistinguishable from that of morpholino-mediated loss of  prdm12  function. In terms of  prdm12b  function, our results indicate that Prdm12b acts as transcriptional repressor and interacts with both EHMT2/G9a and Bhlhe22. However,  bhlhe22  function is not required for  eng1b  expression in vivo, perhaps indicating that other  bhlh  genes can compensate during embryogenesis. Lastly, we do not find evidence for  nkx6.1  and  prdm12b  acting as a repressive pair in formation of the p1 domain – suggesting that  prdm12b  is not solely required to repress non-p1 fates, but is specifically needed to promote p1 fates.    Electronic supplementary material  The online version of this article (10.1186/s13064-019-0129-x) contains supplementary material, which is available to authorized users.

Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain