Differential regulation of the zebrafish orthopedia 1 gene during fate determination of diencephalic neurons.

Differential regulation of the zebrafish orthopedia 1 gene during fate determination of diencephalic neurons.
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DOI:
10.1186/1471-213x-6-50
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发表时间:
2006-10-30
影响因子:
--
通讯作者:
Cotelli F
Cotelli F
中科院分区:
生物学4区
文献类型:
--
作者:
Del Giacco L;Sordino P;Pistocchi A;Andreakis N;Tarallo R;Di Benedetto B;Cotelli F

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同种结构域转录因子骨科(Otp)在限制脊椎动物下丘脑神经内分泌中多类分泌神经元的命运中是必不可少的。然而,关于在发育过程中调控Otp表达的细胞间因子的信息很少。在这里,我们在斑马鱼中确定了两个otp同源基因(otp1和otp2),并在指定神经外胚层区域的形态发生途径的背景下探索了otp1。在前脑发育过程中,otp1在视前区(PO)(前鼻翼板)和后结核(PT)(后基底板)的中脑细胞前群中表达。后一种结构以酪氨酸羟化酶(TH)阳性细胞为特征,表明otp1在儿茶酚胺能(CA)神经元的谱系限制中起作用。Hedgehog (HH)和成纤维细胞生长因子(FGF)通路的中断表明SHH蛋白能够在PO推定的神经母细胞中触发otp1表达,并具有Dzip1和FGF8的减弱作用。此外,我们的数据揭示了otp1是PT中CA神经元的决定因素,其中otp1的活性严格依赖于节点信号,它对SHH和FGF没有反应。在这项研究中,我们确定了otp1转录因子在间脑样本和早期神经元祖细胞状态中的进化重要性。此外,我们的数据表明,形态发生机制在鼻翼和底板中调节otp1的表达存在差异。
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. 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. 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.