Intrinsic and extrinsic regulation of cranial mesoderm

颅内中胚层的内在和外在调节

• 批准号: 6899750
• 负责人: Paul Trainor
• 金额: $ 39.75万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899750
• 关键词: RNA interference; angiogenesis; biological signal transduction; cell growth regulation; cell migration; congenital oral /facial /cranial defect; craniofacial; cytogenetics; embryogenesis; gene expression; histogenesis; laboratory mouse; mesoderm; microarray technology; neural crest; recombinant proteins; RNA interference; angiogenesis; biological signal transduction; cell growth regulation; cell migration; congenital oral /facial /cranial defect; craniofacial; cytogenetics; embryogenesis; gene expression; histogenesis; laboratory mouse; mesoderm; microarray technology; neural crest; recombinant proteins

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rest细胞是一种多能迁移细胞种群，产生大多数骨头，软骨，结缔组织和头部和面部外周神经系统。颅面异常（EX，第一弓综合征，left裂，颅骨症）约占所有先天性异常的三分之一，因此在很大程度上归因于形成，迁移，迁移，增殖和差异的神经克雷斯特细胞的缺陷。为了理解颅面异常的起源并发展干预的治疗方法或方法，这是关键的人类健康问题，了解调节颅神经crest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rest细胞的模式受到神经管形成过程中获得的信号的平衡，以及在迁移和分化过程中接触的组织中收到的信号。颅中胚层是一种与迁移的神经rest细胞广泛相互作用的组织，最近已被证明是在小鼠中神经克雷斯特细胞的身份和迁移特征的构成构成的关键参与者。这认为，颅面异常归因于神经rest细胞发育中的缺陷，通常是颅中胚层等组织中原发性缺陷的次要结果。因此，该提案的主要目标是表征调节颅中胚层模式的固有和外部线索，该提示将为神经rest细胞的发育，颅面形态发生以及颅面异常的起源提供独特的见解。我们正在采用一种免费方法，通过中胚层消融和移植的小鼠中的中胚层特异性基因发现，以及对颅面畸形的小鼠模型的分析，以测试神经Crest Cell，分支拱门和颅骨型的颅胚层的组织和基因特异性功能。