CAREER: Functional Analysis of Crest EffectorS in Craniofacial Development

本奖项全部或部分由《2021年美国救援计划法案》（公法117- 2）资助。在发育和进化生物学领域，一个长期存在的问题是理解动物是如何利用相似的遗传程序发展出不同的外表的。该项目的目标是增强我们对胚胎神经嵴干细胞如何在密切相关的生物体中形成面部组织的认识，以及这些干细胞如何产生不同的外部外观。为了实现这一目标，加州大学戴维斯分校的罗杰斯博士将与主要从本科生和西班牙裔服务机构招募的本科生合作，解剖三种鸟类神经嵴细胞形成的调节程序。这项名为嵴效应功能分析（FACES）的双重研究和教育项目将确定这些蛋白质在胚胎早期表达的变化如何导致鹌鹑、鸡和孔雀胚胎喙结构的差异。罗杰斯博士在研究不同物种的神经嵴细胞和早期发育方面有很强的背景，是世界上为数不多的进行跨物种分析的研究人员之一，以定义鸟类细胞规范和细胞迁移的分子控制。这个教师早期职业发展奖（Career）将资助一个研究和教育项目，为本科生提供专业成长、实践研究机会和长期指导，并将增加我们对脊椎动物胚胎发育过程中复杂组织形成的基本理解。通过提出这个问题，“是什么调节了形成面部的细胞？”我们可以揭开不同物种中驱动面部形成的机制。我们所知道的关于神经嵴发育的大部分信息都是在少数模式生物中独立确定的，这些发现已被纳入神经嵴基因调控网络模型，以解决蛋白质-基因相互作用。然而，我们缺乏跨物种蛋白质功能守恒的确认，从而使对神经嵴进化和发育的全面理解具有挑战性。虽然调节神经嵴发育的因子的表达是保守的，但我们不知道它们是否在相同的发育时间起作用，调节相同的目标，或者这些因子的变化是否驱动物种间的表型差异。本职业将通过定义三种SOXE （sry相关的HMG盒组E）转录因子及其推定靶点I型和II型钙粘蛋白分子在神经嵴细胞及其颅面衍生物形成中的作用，直接解决这一知识障碍。鹌鹑、小鸡和孔雀胚胎将被用来比较表达时间、蛋白质功能和蛋白质扰动对颅面（喙）形成的影响。目的是：1)确定SOXE因子在鸡与鹌鹑胚胎神经嵴（NC）形成和上皮-间质转化（EMT）过程中的作用；2)确定控制鸡与鹌鹑胚胎NC细胞命运和EMT的钙粘蛋白编码；3)量化SOXE和钙粘蛋白干扰对颅面喙结构的影响。总的来说，这项工作将阐明驱动神经嵴细胞形成的分子、细胞和有机体水平机制，并将显著增加我们对生物体如何使用相同因素驱动不同形态发生的理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117- 2).A long-standing question in the fields of developmental and evolutionary biology is to understand how animals develop different outer appearances using similar genetic programs. The goal of this project is to enhance our knowledge of how embryonic neural crest stem cells form the tissues that make the face in closely related organisms, and how these stem cells give rise distinct outer appearances. To achieve this goal, Dr. Rogers at UC Davis will work with undergraduate students recruited from primarily undergraduate and Hispanic-serving institutions to dissect the programs that regulate the formation of neural crest cells in three bird species. The dual research and educational project called Functional Analysis of Crest EffectorS (FACES), will identify how changing the expression of these proteins at early embryonic stages drives differences in beak structure in quail, chicken, and peafowl embryos. Dr. Rogers has a strong background in studying neural crest cells and early development across various species, and is one of the few investigators in the world performing cross-species analyses to define the molecular control of cell specification and cell migration in avians. This faculty Early Career Development Award (CAREER) will fund a research and educational program that provides professional growth, hands-on research opportunities and long-term mentoring for undergraduate students, and will increase our fundamental understanding of how complex tissues are formed during vertebrate embryonic development. By asking the question, “what regulates the cells that make the face?” we can unravel the mechanisms driving formation of faces in different species. Much of the information we know about neural crest development has been identified independently in a handful of model organisms, and the findings have been incorporated into a neural crest gene regulatory network model to resolve protein-gene interactions. However, we lack confirmation of the functional conservation of proteins across species, thereby making comprehensive understanding of neural crest evolution and development challenging. Although the expression of the factors that regulate neural crest development are conserved, we do not know if they function at the same developmental time, regulate the same targets, or if changes in these factors drive phenotypic variation across species. This CAREER will directly address this barrier to knowledge by defining the roles of three SOXE (SRY-related HMG box Group E) transcription factors, and their putative targets, type I and II cadherin molecules, in the formation of neural crest cells and their craniofacial derivatives. Quail, chick, and peafowl embryos will be used to compare expression timing, protein function, and outcome of protein perturbations on craniofacial (beak) formation. The objectives are to 1) identify the roles of SOXE factors during neural crest (NC) specification and the epithelial-mesenchymal transition (EMT) in chick versus quail embryos, 2) determine the cadherin code that controls NC cell fate and EMT in chick vs quail, and 3) quantify the effects of SOXE and cadherin perturbations on craniofacial beak structure. Collectively, this work will shed light on the molecular, cellular, and organismal-level mechanisms that drive neural crest cell formation and will significantly increase our understanding of how organisms use the same factors to drive differential morphogenesis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.