NSF Postdoctoral Fellowship in Biology FY 2021: Identifying the functional roles of SNAI2,SOX9, and SOX10 in cranial neural crest cell specification and adhesion

该行动为2020财年美国国家科学基金会生物学博士后研究奖学金提供资金，扩大生物学中代表性不足群体的参与。该奖学金支持研究员的研究和培训计划，该计划将增加在生物学中代表性不足的群体的参与。这位研究员提出要了解细胞如何在整个发育中的胚胎体中移动，以便在正确的时间到达正确的目的地。这项研究将使用模式生物来了解这些细胞的功能，因为这个过程在物种之间是保守的。将被检查的特定细胞是那些形成头部和面部特征的细胞，因为这个过程中的任何轻微破坏都可能导致各种出生缺陷，包括唇裂。通过了解这些细胞在模式生物中的运动和功能，这项研究可能有助于理解和开发针对这些出生缺陷的新疗法。此外，该项目将通过一个新颖的校园学生和博士后组织，为生物学中代表性不足的群体提供获得科学、专业和个人支持的机会，从而扩大他们的参与。神经嵴（NC）细胞发育是一个高度动态的过程，受严格调控的基因调控网络（GRN）控制，GRN驱动几种转录因子的表达，这些转录因子驱动细胞的命运、迁移和分化。SOX9和SNAI2在上皮-间质转化中起作用，其次是介导NC细胞迁移的SOX10。编码这些NC转录因子的基因在NC发育过程中表达，但对SNAI2、SOX9和SOX10在相互调节表达中的保守作用知之甚少，也不知道它们如何特异性控制NC细胞群中相关钙粘附蛋白的表达。因此，本研究拟在鸡和鹌鹑两种互补的羊膜模型中确定三种高表达的NC细胞指示物（SNAI2、SOX9和SOX10）是如何驱动NC规范和调节NC粘附的。目的1将确定NC发育过程中SNAI2、SOX9和SOX10蛋白的时空定位，并确定SOX9、SOX10和SNAI2功能扰动对体内钙粘蛋白的影响及其后果。目的2将确定SOX9、SOX10和SNAI2在鸡和鹌鹑中的结合伙伴，并表征SNAI2、SOX9和SOX10蛋白结构域的功能。该项目将有助于在以下领域培训研究员：科学写作，技术技能，指导和教学。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 action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2020, Broadening Participation of Groups Under-represented in Biology. The Fellowship supports a research and training plan for the Fellow that will increase the participation of groups underrepresented in biology. The fellow proposes to understand how cells move throughout the developing embryo body to reach the right destination at the right time. This research will use model organisms to understand how these cells function, as this process is conserved across species. The specific cells that will be examined are those that form the head and facial features, as any minor disruptions in this process can lead to a variety of birth defects, including cleft lip. By understanding how these cells move and function in a model organism, the research can potentially contribute to the understanding and development of novel therapies for these birth defects humans. In addition, this project will broaden the participation of under-represented groups in biology by providing the opportunity for them to receive scientific, professional, and personal support through a novel on-campus student and postdoc organization. Neural crest (NC) cell development is a highly dynamic process that is controlled by a tightly regulated gene regulatory network (GRN) which drives the expression of several transcription factors that drive cell fate, migration, and differentiation. SOX9 and SNAI2 function in the epithelial-mesenchymal transition, followed by SOX10 which mediates NC cell migration. The genes that code for these NC transcription factors are expressed during NC development, but little is known about the conserved roles of SNAI2, SOX9, and SOX10 in regulating the expression of each other nor how they specifically control expression of relevant cadherin proteins in the NC cell population. Therefore, this research proposes to determine how three of the most highly expressed NC cell specifiers (SNAI2, SOX9, and SOX10) drive NC specification and regulate NC adhesion in two complementary amniote models, Gallus gallus (chicken) and Coturnix japonica (quail). Aim 1 will define the spatiotemporal localization of SNAI2, SOX9, and SOX10 proteins during NC development and identify the effects of SOX9, SOX10, and SNAI2 functional perturbations and their consequences on cadherin proteins in vivo. Aim 2 will determine the binding partners of SOX9, SOX10 and SNAI2 in chick and quail and characterize SNAI2, SOX9, and SOX10 protein domain functions. This project will contribute to training of the fellow in the following areas: scientific writing, technical skills, mentoring, and teaching.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.