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的迁移细胞群，它产生了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（如第一弓综合征、腭裂、颅缝闭）约占所有先天性异常的三分之一，因此主要归因于神经嵴细胞的形成、迁移、增殖和分化缺陷。为了了解颅面异常的起源并开发治疗或干预方法，这是人类健康的关键问题，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在其形成过程中获得的信号以及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。颅中胚层是一种与迁移的神经嵴细胞广泛相互作用的组织，最近已被证明在小鼠神经嵴细胞的身份和迁移特征中起着关键作用。这表明颅面畸形是由于神经嵴细胞发育缺陷引起的，通常可能是颅中胚层等组织的原发性缺陷的继发后果。因此，本研究的主要目标是描述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。我们采用一种互补的方法，通过对中胚层切除和移植的小鼠进行基因芯片阵列发现中胚层特异性基因，并对小鼠颅面畸形模型进行分析，以测试神经嵴细胞、鳃弓和颅面发育过程中颅中胚层的组织和基因特异性功能。

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.