Abstract
BackgroundThe 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.ResultsHere, 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.ConclusionIn 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.
Highlights
The homeodomain transcription factor Orthopedia (Otp) is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates
In this paper we provide strong circumstantial evidence of regulatory links between otp1 expression and Nodal, SHH and Fibroblast Growth Factor (FGF) signaling cascades in the hypothalamus
The first piece of evidence demonstrates that Nodal, in concert with fgf8 and shh, mediates otp1 expression in the preoptic area (Fig. 11)
Summary
The homeodomain transcription factor Orthopedia (Otp) is essential in restricting the fate of multiple classes of secreting neurons in the neuroendocrine hypothalamus of vertebrates. Knowledge of the mechanisms of action connecting the prosencephalic signaling pathways, the expression of specific transcription factors and the specification of neuronal individuality during the development of the hypothalamus remains largely unclear [15]. A congenital disorder with deficiencies in specific groups of CA neurons, are characterized by disruption of sonic hedgehog (shh) and secondary down-regulation of otp, brn and sim, evoking an interaction between otp and shh [36]. Despite all these evidences, the mechanisms of regulation of the Otp gene itself remain largely obscure
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