RUI: Analysis of the role of Wntless in regulating Wnt gradient formation

胚胎的正常发育依赖于众多信号的协调和整合。WNT蛋白代表这样一类信号，在许多不同的发育过程中都是必需的，包括脑、脊髓、肾脏、四肢、肺、皮肤、骨骼、性腺、眼睛、耳朵和肌肉发育。当正常发挥功能时，Wnt蛋白从细胞中分泌出来，并形成细胞外浓度梯度，其典型特征是随着距离的推移，浓度逐渐下降。这种梯度的形状和长度对靶细胞对Wnt信号的反应方式有深远的影响。这项工作的目标是确定Wnless的作用，Wnless是一种已知的调节Wnt蛋白的活性和分布的蛋白质。特别是，这个项目将研究Wnless在确定WNT渐变的形状和长度方面所起的作用。这些研究完成后，将对形成梯度的分子机制有更好的理解。这些数据将与我们对胚胎发育的理解相关，并可能对与出生缺陷和其他Wnt信号调控不当的疾病相关的研究产生广泛的影响。重要的是，这项研究的资金将为旧金山州立大学多达12名本科生和硕士学生提供研究培训机会，旧金山州立大学拥有异常丰富和多样化的学生群体。

The proper development of an embryo relies on the coordination and integration of numerous signals. Wnt proteins represent one such class of signals and are required for many different developmental processes including brain, spinal cord, kidney, limb, lung, skin, bone, gonad, eye, ear, and muscle development. When properly functioning, Wnt proteins are secreted from cells and form an extracellular concentration gradient that is typified by a graded decline in concentration over distance. The shape and the length of this gradient have profound effects on the way that target cells respond to the Wnt signal. The goal of this work is to define the role of Wntless, a protein that is known to regulate the activity and distribution of Wnt proteins. In particular, this project will examine the role of Wntless in establishing the shape and length of the Wnt gradient. Upon the completion of these studies, a better understanding of the molecular mechanisms by which gradients are formed will be gained. These data will have relevance to our understanding of embryonic development and may have broad implications for research pertaining to birth defects and other diseases in which Wnt signaling is improperly regulated. Importantly, funding for this research will provide research-training opportunities for up to 12 undergraduate and Masters students at San Francisco State University, which has an unusually rich and diverse student population.