Intrinsic and extrinsic regulation of cranial mesoderm

颅内中胚层的内在和外在调节

基本信息

批准号：
7456417
负责人：
Paul Trainor
金额：
$ 37.28万
依托单位：
STOWERS INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7456417
关键词：
Ablation Accounting Address Anterior Antibodies Biological Assay Blood Vessels Bone and Cartilage Funding Branchial arch structure Cells Cephalic Characteristics Chemicals Chick Embryo Cleft Palate Commit Complex Connective Tissue Craniofacial Abnormalities Craniosynostosis Cues Defect Development Differentiation and Growth Ectoderm Embryo Endoderm Endothelial Cells Equilibrium Exhibits Face Gene Chips Genes Genetic Genetic Programming Goals Goldenhar Syndrome Head Health Human In Vitro Intervention Mesoderm Methods Molecular Morphogenesis Mus Mutant Strains Mice Nerve Neural Crest Neural Crest Cell Neural tube Pattern Peripheral Nervous System Plastics Population Process Protein Overexpression Purpose RNA Interference Recombinant Proteins Regulation Rest Rodent Role Signal Pathway Signal Transduction Somites Staging Technology Testing Tissues Translating Transplantation Ultrasonography Viral angiogenesis craniofacial day embryo culture gene discovery in utero inhibitor/antagonist insight malformation migration mouse model novel spatiotemporal vasculogenesis

项目摘要

DESCRIPTION (provided by applicant): Cranial neural crest cells are a multipotent migratory cell population which generate the majority of the bone, cartilage, connective tissue and peripheral nervous system of the head and face. Craniofacial abnormalities (ex, first arch syndrome, cleft palate, craniosynostoses) account for approximately one-third of all congenital anomalies and therefore are largely attributable to defects in the formation, migration, proliferation and differentiation of neural crest cells. In order to comprehend the origins of craniofacial abnormalities and develop treatments or methods of intervention, which are critical human health issues, it is vital to understand the genetic and cellular mechanisms that regulate cranial neural crest cell and head development. Sophisticated genetic and cellular analyses have determined that neural crest cell patterning is governed by a balance of signals acquired in the neural tube during their formation together with signals received from the tissues they contact during their migration and differentiation. The cranial mesoderm is one such tissue that interacts extensively with the migrating neural crest cells and recently has been demonstrated to be a key player in patterning both the identity and migration characteristics of neural crest cells in mice. This argues that craniofacial abnormalities, which are attributed to defects in neural crest cell development, may often be the secondary consequence of primary defects in tissues such as the cranial mesoderm. Therefore, the primary goal of this proposal is to characterize the intrinsic and extrinsic cues that regulate cranial mesoderm patterning which will provide unique insights into neural crest cell development, craniofacial morphogenesis, and the origins of craniofacial abnormalities. We are taking a complimentary approach combining mesoderm specific gene discovery via gene chip arrays in mice with mesoderm ablations and transplantations together with analyses in mouse models of craniofacial malformation to test for tissue and gene specific function of the cranial mesoderm during neural crest cell, branchial arch, and craniofacial development.

描述（由申请人提供）：颅神经嵴细胞是一种多能迁移细胞群，其产生头部和面部的大部分骨骼、软骨、结缔组织和周围神经系统。颅面异常（例如，第一弓综合征、腭裂、颅缝早闭）约占所有先天性异常的三分之一，因此很大程度上归因于神经嵴细胞的形成、迁移、增殖和分化缺陷。为了了解颅面异常的起源并开发治疗或干预方法（这是人类的关键健康问题），了解调节颅神经嵴细胞和头部发育的遗传和细胞机制至关重要。复杂的遗传和细胞分析已经确定，神经嵴细胞的模式是由神经管形成过程中获得的信号与它们在迁移和分化过程中接触的组织接收到的信号的平衡控制的。颅中胚层是一种与迁移的神经嵴细胞广泛相互作用的组织，最近被证明是小鼠神经嵴细胞的身份和迁移特征模式的关键参与者。这表明，由于神经嵴细胞发育缺陷而导致的颅面异常，通常可能是颅内中胚层等组织原发性缺陷的继发后果。因此，该提案的主要目标是表征调节颅中胚层模式的内在和外在线索，这将为神经嵴细胞发育、颅面形态发生和颅面异常的起源提供独特的见解。我们正在采取一种互补的方法，通过中胚层消融和移植的小鼠基因芯片阵列发现中胚层特异性基因，并结合颅面畸形小鼠模型的分析，以测试颅面中胚层在神经嵴细胞、鳃弓期间的组织和基因特异性功能和颅面发育。