Intrinsic and extrinsic regulation of cranial mesoderm

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、软骨、结缔组织和周围神经系统。颅面畸形（例如，第一弓综合征、腭裂、颅缝早闭）约占所有先天性畸形的三分之一，因此主要归因于神经嵴细胞的形成、迁移、增殖和分化缺陷。为了理解颅面异常的起源并开发治疗或干预方法，这是关键的人类健康问题，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，神经嵴细胞的图案化是由在其形成过程中在神经管中获得的信号与在其迁移和分化过程中从其接触的组织接收的信号的平衡所控制的。颅中胚层是一个这样的组织，广泛地与迁移的神经嵴细胞相互作用，最近已被证明是一个关键的球员在图案的身份和迁移特性的神经嵴细胞在小鼠。这表明，颅面畸形，这是由于神经嵴细胞发育的缺陷，可能往往是继发性的组织，如颅中胚层的主要缺陷。因此，这项建议的主要目标是表征内在和外在的线索，调节颅中胚层图案，这将提供独特的见解神经嵴细胞发育，颅面形态发生，颅面异常的起源。我们正在采取一种互补的方法，结合中胚层特异性基因的发现，通过基因芯片阵列在小鼠中的中胚层消融和移植，在颅面畸形的小鼠模型分析，以测试颅中胚层的组织和基因特异性功能，在神经嵴细胞，鳃弓，颅面发育。

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.