Developmental Biology Unit, Faculty of Biology, and BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
PLoS One. 2013 Sep 20;8(9):e75002. doi: 10.1371/journal.pone.0075002. eCollection 2013.
The homeodomain transcription factor Orthopedia (Otp) is an important regulator for specification of defined subsets of neuroendocrine cells and dopaminergic neurons in vertebrates. In zebrafish, two paralogous otp genes, otpa and otpb, are present in the genome. Neither complete loss of Otp activity nor differential contributions of Otpa and Otpb to specification of defined neuronal populations have been analyzed in detail. We characterized zebrafish embryos and early larvae mutant for null alleles of otpa, otpb, or both genes to determine their individual contributions to the specification of th expressing dopaminergic neuronal populations as well as of crh, oxt, avp, trh or sst1.1 expressing neuroendocrine cells. otpa mutant larvae show an almost complete reduction of ventral diencephalic dopaminergic neurons, as reported previously. A small reduction in the number of trh cells in the preoptic region is detectable in otpa mutants, but no significant loss of crh, oxt and avp preoptic neuroendocrine cells. otpb single mutant larvae do not display a reduction in dopaminergic neurons or neuroendocrine cells in the otp expressing regions. In contrast, in otpa and otpb double mutant larvae specific groups of dopaminergic neurons as well as of crh, oxt, avp, trh and sst1.1-expressing neuroendocrine cells are completely lost. These observations suggest that the requirement for otpa and otpb function during development of the larval diencephalon is partially redundant. During evolutionary diversification of the paralogous otp genes, otpa maintained the prominent role in ventral diencephalic dopaminergic and neuroendocrine cell specification and is capable of partially compensating otpb loss of function. In addition, we identified a role of Otp in the development of a domain of somatostatin1-expressing cells in the rostral hindbrain, a region with strong otp expression but so far uncharacterized Otp function. Otp may thus be crucial for defined neuronal cell types also in the hindbrain.
同源盒转录因子 Orthopedia（Otp）是脊椎动物中特定神经内分泌细胞和多巴胺能神经元的重要调节因子。在斑马鱼中，基因组中存在两个同源的 otp 基因，otpa 和 otpb。尚未详细分析 Otp 活性完全丧失或 Otpa 和 Otpb 对特定神经元群体的贡献差异。我们对 otpa、otpb 或这两个基因的缺失等位基因的斑马鱼胚胎和早期幼虫进行了特征描述，以确定它们对表达 dopaminergic 神经元群体以及 crh、oxt、avp、trh 或 sst1.1 表达的神经内分泌细胞的特定贡献。otpa 突变体幼虫表现出腹侧神经上皮多巴胺能神经元的几乎完全缺失，如先前报道的那样。在 otpa 突变体中可检测到前脑区 trh 细胞数量略有减少，但 crh、oxt 和 avp 前脑神经内分泌细胞没有明显丢失。otpb 单突变体幼虫在表达 otp 的区域中没有减少多巴胺能神经元或神经内分泌细胞。相比之下，在 otpa 和 otpb 双突变体幼虫中，特定的多巴胺能神经元群体以及 crh、oxt、avp、trh 和 sst1.1 表达的神经内分泌细胞完全缺失。这些观察结果表明，otpa 和 otpb 功能在幼虫间脑发育过程中的需求部分冗余。在同源 otp 基因的进化多样化过程中，otpa 保持了在腹侧神经上皮多巴胺能和神经内分泌细胞特异性中的突出作用，并能够部分补偿 otpb 功能丧失。此外，我们还确定了 Otp 在发育中的作用 rostral hindbrain 中 somatostatin1 表达细胞的一个区域，该区域具有强烈的 otp 表达，但到目前为止功能未知。因此，Ot 可能对后脑的特定神经元细胞类型也很重要。
