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Protein/nucleic Acid Interactions In Vertebrate Embryogenesis

脊椎动物胚胎发生中的蛋白质/核酸相互作用

基本信息

批准号：
8941451
负责人：
THOMAS D sargent
金额：
$ 60.7万
依托单位：
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8941451
关键词：
Affect Animal Model Biological Assay Cell-Cell Adhesion Cephalic Congenital Abnormality Craniofacial Abnormalities Defect Development Diagnostic Distal Dominant-Negative Mutation Dysmorphology Embryo Embryonic Development Epidermis Experimental Models Face Failure Family Fishes Fresh Water Gene Expression Profile Gene Expression Profiling Gene Targeting Genes Genetic Goals Head Human Infant Jaw Laboratories Lead Link Mus Mutate Mutation Myeloid Cells Nature Neural Crest Neural Crest Cell Nucleic Acids Oligonucleotides Outcome Peripheral Nervous System Phenotype Play Protein Kinase Proteins Rana Regulation Research Role Shapes Skeleton Staging TFAP2A gene Technology Testing Therapeutic Tissues Transgenic Organisms Work Xenopus Zebrafish base blastomere structure cell motility cell type craniofacial design gene discovery gene function genome-wide homeodomain loss of function migration prevent research study tool transcription factor

项目摘要

The neural crest (NC) plays a critical role in the developmental of the vertebrate head, face and jaws, providing the bulk of the craniofacial skeleton as well as peripheral nervous system and other cranial tissues. Normal craniofacial development depends on proper induction, migration and differentiation of NC cells and derivatives. Deficiencies at any of these steps, whether due to intrinsic defects in NC itself, or in failure of NC cells to interact properly with adjacent tissues, can lead to birth defects: up to a third of all congenital malformations are craniofacial in nature and mostly due to such NC failures. We have used the frog Xenopus and the freshwater tropical fish Danio rerio(zebrafish)as experimental model organisms to study NC development. The starting point for this project was two transcription factors, TFAP2a and Dlx3, the regulation of which we showed several years ago to be critical for the early steps in NC development. We are now designing, establishing and using transgenic zebrafish lines expressing both wild-type and mutated versions of these factors, followed by morphological and gene expression analysis, to identify target genes for these factors, and also to study their function in later stages of neural crest migration and terminal differentiation. Our goal is to relate the regulation of specific genes by TFAP2 and Dlx factors to cranifacial development in human embryos, both normal and pathological, hoping to establish diagnostic tools and, eventually, therapeutic strategies for preventing and treating cranifacial dysmorphology, the most common form of birth defects in human infants.

神经嵴（NC）在脊椎动物头、脸和颌的发育中起着至关重要的作用，它提供了颅面骨骼以及周围神经系统和其他颅组织的主体。正常颅面发育依赖于NC细胞及其衍生物的适当诱导、迁移和分化。这些步骤的任何缺陷，无论是由于NC本身的内在缺陷，还是NC细胞无法与邻近组织正常相互作用，都可能导致出生缺陷：多达三分之一的先天性畸形本质上是颅面畸形，而且主要是由于NC失败。我们以爪蟾和淡水热带鱼斑马鱼作为实验模式生物，研究了NC的发育。这个项目的起点是两个转录因子，TFAP2a和Dlx3，我们几年前就证明了它们的调控对NC发展的早期阶段至关重要。