Induktion des Telencephalons in der Zebrafisch Entwicklung

在脊椎动物发育过程中，位于神经板最亲侧的简单上皮细胞片分化为前脑，这是已知的最复杂的细胞结构之一。虽然有几个关键因素被证明参与了端脑命运的诱导，但我们还远远不了解这个分子网络（相互作用）是如何实现这种形态复杂性的。我们的研究旨在揭示BMP信号活动在神经板发育中的作用，并试图揭示斑马鱼和其他脊椎动物早期端脑D/V模式事件中涉及的新网络成分。首先，我将通过使用热休克诱导的显性阴性和构成活性BMP受体转基因系来表征神经板（新生端脑）中BMP信号活动的时空功能。此外，我将评估BMP和Wnt信号通路活性在ANB形成和端脑顶信号中心建立中的潜在组合效应。与此同时，将进行无偏倚的基于DNA阵列的转录组分析，以筛选在神经发育期间限制预期背侧或腹侧端脑区域的因素。我希望在将端脑区域化为苍白质和亚苍白质的过程中，分离出参与早期命运决定的新因素。最后，我将通过对鱼、鸡和小鼠早期前脑标记物的比较表达分析，开始解决神经板模式机制的进化保护问题。

During vertebrate development a simple epithelial sheet of cells, located at the most rostral part of the neural plate, differentiates into the forebrain, one of most complex cellular structures known. Although several key factors have been shown to be involved in the induction of telencephalic fate, we are far from understanding how this molecular network (inter)acts to achieve such a morphological complexity. Our proposal aims to disclose the role of BMP signalling activity in neural plate development and intends to unravel new network components involved in early telencephalic D/V patterning events in zebrafish and other vertebrates. First I will characterize the spatial-temporal function of BMP signalling activity in the neural plate (nascent telencephalon) by using heat shock inducible dominant negative and constitutively active BMP receptor transgenic lines. Additionally I will assess the potential combinatorial effect of BMP and Wnt signalling pathway activity in ANB formation and establishment of telencephalic roof signalling centre. In parallel an unbiased DNA array-based transcriptome analysis will be performed to screen for factors restricted to the prospective dorsal or ventral telencephalic territories during neurulation. I expect to isolate new factors involved in early fate decisions during regionalization of the telencephalon into pallium and sub-pallium. Finally, I will begin to address the evolutionary conservation of neural plate patterning mechanisms by performing a comparative expression analysis of early forebrain markers in fish, chick and mouse.