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Tissue-specific regulation of cellular morphogenesis during embryonic development of the invertebrate chordate Ciona intestinalis

无脊椎动物脊索动物胚胎发育过程中细胞形态发生的组织特异性调节

基本信息

批准号：
9763586
负责人：
Alberto Stolfi
金额：
$ 12.97万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-05 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9763586
关键词：
Animal Model Applications Grants Award Behavior Biological Assay CRISPR/Cas technology Candidate Disease Gene Cardiac Cardiac development Cell physiology Cells Child Chordata Ciona intestinalis Communities Complex Cues Data Development Embryo Embryonic Development Fluorescence-Activated Cell Sorting Foundations Gene Expression Regulation Genes Genetic Transcription Heart Human Image Analysis Imaging Techniques Individual Instruction Invertebrates Learning Mediating Mentors Molecular Morphogenesis Morphology Movement Muscle Mutagenesis Nervous system structure Neurites Neuronal Differentiation Neurons Organ Orthologous Gene Outcome Pattern Phase Postdoctoral Fellow Process Property Regulation Research Research Personnel Role Shapes Stereotyping Syndrome System Tadpoles Tail Testing Tissues Training Urochordata Vertebrates Work candidate identification cell behavior cell growth regulation cell type developmental genetics embryo cell experimental study follow-up gene function graduate student human disease interest loss of function mutation migration neurodevelopment post-doctoral training progenitor programs public health relevance quantitative imaging relating to nervous system skills tool transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): I am broadly interested in gene regulation and cellular processes that are instructive for embryonic development. As a graduate student, I made several discoveries relating to the specification, patterning, and morphogenesis of embryonic neural and cardiac progenitors in the tunicate Ciona intestinalis. Recognizing the largely untapped potential of Ciona and other tunicates as model organisms for developmental genetics, I have continued my postdoctoral research working on these invertebrate chordates. During my post-doc, I have developed additional tools for the study of gene function in Ciona and established myself as a young leader of the tunicate research community. The K99/R00 award will allow me to complete my formal training and begin my transition to a role as an independent investigator, at the helm of a research group studying cellular morphogenesis in tunicate embryonic development. For this project, I propose to study gene function in regulation of migration and polarization of two distinct cell types in the Ciona embryo, the Trunk Ventral Cells (TVCs) and the Bipolar Tail Neurons (BTNs). In the K99 mentored phase, I will first investigate gene function by CRISPR/Cas9- mediated mutagenesis in the TVCs, which undergo stereotyped directed migration and polarity orientation. I will then profile the transcriptome of te BTNs, identifying Candidate genes that may regulate stereotyped directed migration and orientation of polarity. The completion of these aims will prepare me for pursuing my third aim, to be performed in the R00 mentored phase, of testing the requirement for those Candidate genes in the BTNs, allowing for direct comparisons between the molecular control of migration and polarity in different cell types in different niches of the same embryo. The mentored phase fits the research interests of both my mentor, Dr. Christiaen, and I. We both aim to understand how cell behavior is regulated, and how deficiencies in this regulatory control may result in developmental syndromes and human disease. Where I hope to distinguish myself from my mentor during the independent phase and beyond is in my particular interest in neural development and neuronal differentiation, in contrast to Dr. Christiaen's focus on cardiac development. The K99 award will allow me to complete my postdoctoral training, by learning and meaningfully applying FACS, RNA-seq, and automated imaging techniques. The K99 will also enable me to generate preliminary data that I can take with me as the foundation for an independent research program.

描述（由申请人提供）：我对胚胎发育的基因调控和细胞过程有广泛的兴趣。作为一名研究生，我在被囊玻璃海鞘的胚胎神经和心脏祖细胞的规格，模式和形态发生方面有了几个发现。认识到玻璃海鞘和其他被囊动物作为发育遗传学模式生物的巨大潜力，我继续从事这些无脊椎脊索动物的博士后研究。在我的博士后期间，我开发了更多的工具来研究玻璃海鞘的基因功能，并成为被囊动物研究界的年轻领导者。K99/R 00奖将使我能够完成我的正式培训，并开始我作为一个独立的研究者角色的过渡，在一个研究组研究细胞形态发生在被囊动物胚胎发育的掌舵。对于这个项目，我建议研究基因功能的调节迁移和极化的两种不同类型的细胞在玻璃海鞘胚胎，干细胞（TVC）和双极尾神经元（BTNs）。在K99指导阶段，我将首先通过CRISPR/Cas9介导的TVC诱变研究基因功能，TVC经历定型定向迁移和极性取向。然后，我将分析BTNs的转录组，确定可能调节定型定向迁移和极性方向的候选基因。这些目标的完成将使我为追求我的第三个目标做好准备，该目标将在R 00指导阶段执行，即测试BTNs中对这些候选基因的需求，从而可以直接比较同一胚胎不同小生境中不同细胞类型中迁移和极性的分子控制。指导阶段符合我的导师Christiaen博士和我的研究兴趣。我们都旨在了解细胞行为是如何调节的，以及这种调节控制的缺陷如何导致发育综合征和人类疾病。我希望在独立阶段及以后与我的导师区分开来的地方是我对神经发育和神经元分化特别感兴趣，而不是Christiaen博士对心脏发育的关注。 K99奖将使我能够完成我的博士后培训，通过学习和有意义地应用FACS，RNA-seq和自动成像技术。K99还将使我能够生成初步数据，这些数据可以作为独立研究计划的基础。