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CAREER: Functional Analysis of Crest EffectorS in Craniofacial Development

职业：颅面部发育中嵴效应器的功能分析

基本信息

批准号：
2143217
负责人：
Crystal Rogers
金额：
$ 125.75万
依托单位：
University of California-Davis
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143217&HistoricalAwards=false
关键词：
CAREER Functional Analysis Crest EffectorS

项目摘要

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.

该奖项全部或部分由2021年美国救援计划法案（公法117- 2）资助。发育和进化生物学领域的一个长期存在的问题是了解动物如何使用相似的遗传程序发展不同的外观。该项目的目标是提高我们对胚胎神经嵴干细胞如何形成在密切相关的生物体中形成面部的组织的知识，以及这些干细胞如何产生独特的外观。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，解剖调节三种鸟类神经嵴细胞形成的程序。这项双重研究和教育项目名为“冠状动脉功能分析”（FACES），将确定在早期胚胎阶段改变这些蛋白质的表达如何驱动鹌鹑、鸡和孔雀胚胎中喙结构的差异。罗杰斯博士在研究神经嵴细胞和不同物种的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以确定鸟类细胞规格和细胞迁移的分子控制的研究人员之一。该教师早期职业发展奖（CAREER）将资助一项研究和教育计划，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。通过问这样一个问题，“是什么调节了构成面部的细胞？”我们就能解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已经在少数模式生物中独立鉴定，并且这些发现已经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，我们缺乏跨物种的蛋白质的功能保护的确认，从而使全面了解神经嵴的进化和发展具有挑战性。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，调节相同的靶点，或者这些因子的变化是否会导致物种间的表型变异。这个职业生涯将通过定义三个SOXE（SRY相关的HMG盒E组）转录因子的作用直接解决这一知识障碍，以及它们的假定靶点，I型和II型钙粘蛋白分子，在神经嵴细胞及其颅面衍生物的形成中。鹌鹑、小鸡和孔雀胚胎将用于比较表达时间、蛋白质功能以及蛋白质扰动对颅面（喙）形成的结果。目的是1）确定SOXE因子在鸡与鹌鹑胚胎神经嵴（NC）特化和上皮-间质转化（EMT）过程中的作用，2）确定控制鸡与鹌鹑NC细胞命运和EMT的钙粘蛋白密码，3）量化SOXE和钙粘蛋白扰动对颅面喙结构的影响。总的来说，这项工作将揭示驱动神经嵴细胞形成的分子，细胞和生物体水平的机制，并将显着增加我们对生物体如何使用相同的因素来驱动差异形态发生的理解。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。