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Background  The homeodomain transcription factor Orthopedia (Otp) is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates. However, there is little information on the intercellular factors that regulate  Otp  expression during development.    Results  Here, we identified two  otp  orthologues in zebrafish ( otp1  and  otp2 ) and explored  otp1  in the context of the morphogenetic pathways that specify neuroectodermal regions. During forebrain development,  otp1  is expressed in anterior groups of diencephalic cells, positioned in the preoptic area (PO) (anterior alar plate) and the posterior tuberculum (PT) (posterior basal plate). The latter structure is characterized by Tyrosine Hydroxylase (TH)-positive cells, suggesting a role for  otp1  in the lineage restriction of catecholaminergic (CA) neurons. Disruptions of Hedgehog (HH) and Fibroblast Growth Factor (FGF) pathways point to the ability of SHH protein to trigger  otp1  expression in PO presumptive neuroblasts, with the attenuating effect of Dzip1 and FGF8. In addition, our data disclose  otp1  as a determinant of CA neurons in the PT, where  otp1  activity is strictly dependent on Nodal signaling and it is not responsive to SHH and FGF.    Conclusion  In this study, we pinpoint the evolutionary importance of  otp1  transcription factor in cell states of the diencephalon anlage and early neuronal progenitors. Furthermore, our data indicate that morphogenetic mechanisms differentially regulate  otp1  expression in alar and basal plates.

Differential regulation of the zebrafish orthopedia1 gene during fate determination of diencephalic neurons