ROLES OF CHORDIN AND NOGGIN IN CRANIOFACIAL DEVELOPMENT

描述（改编自研究者摘要）：颅面 发育是脊椎动物个体发育中独特复杂的形态发生过程， 创造了进化的可塑性，但也创造了发育的脆弱性。头部 和脸是来自许多组织前体，这需要一个精确的 模式形成、细胞迁移、增殖、凋亡 和诱导相互作用来实现功能性目的。这些事件中的许多事件 是由分泌的细胞因子介导的，其活性必须被精确地调节 以防止不适当的细胞反应。骨形态发生蛋白 骨形成蛋白（BMPs）是一个分泌型配体家族，其对许多骨形成蛋白具有强效作用。 颅面发育的各个方面，特别是与颅面发育密切相关的蛋白质， BMP 2和BMP 4。他们的活动被认为是重要的增长或 大脑、头骨、脑垂体等不同组织的图案 牙齿，以及面部的前体。果蝇的研究， 非洲爪蟾的研究表明，BMP 2/4信号转导在很大程度上受 拮抗蛋白如Chordin（Chd）和Noggin（Nog）。在青蛙中， Nog促进前部发育，Chd是正常头部所必需的 斑马鱼的发育本提案中描述的初步工作表明， 这些基因是哺乳动物头部发育所必需的。缺乏 先天性心脏病在近交遗传背景下导致一组颅面骨骼 和涉及神经嵴衍生物的软组织缺损，类似于那些 出现在某些人类综合症中。Chd和Nog一起被要求在早期 头部的发展，但也参与具体的发展， 前脑，嘴，鼻子，下颌骨，头骨的许多骨头，和其他 颅面组织该提案的主要目的是：1）描述 Chd和Nog的时空表达模式，以阐明其在 颅面发育; 2）确定关键部位和时间 Chd和Nog在使用胚胎干细胞嵌合体的头部诱导中的作用， 组织重组体; 3）确定这些基因在生长中的功能， 颅面组织的图案化;以及4）评估异位BMP是否 信号传导再现了突变体的颅面缺陷。

DESCRIPTION (Adapted from the Investigator's Abstract): Craniofacial development is a uniquely complex morphogenetic process in vertebrate ontogeny, creating evolutionary plasticity but also developmental vulnerability. The head and face are derived from many tissue precursors, which require a precise orchestration of pattern formation, cell migration, proliferation, apoptosis, and inductive interactions to achieve a functional end. Many of these events are mediated by secreted cytokines, whose activity must be precisely regulated to preclude inappropriate cellular responses. Bone Morphogenetic Proteins (BMPs) are a family of secreted ligands which have potent effects on many aspects of craniofacial development, particularly the closely related proteins BMP2 and BMP4. Their activity is thought to be important in the growth or patterning of such diverse tissues as the brain, the skull, the pituitary gland, the teeth, and the precursors of the face. Research from Drosophila and Xenopus indicate that BMP2/4 signal transduction is regulated in large part by antagonistic proteins such as Chordin (Chd) and Noggin (Nog). In frogs, Chd and Nog promote anterior development, and Chd is essential for normal head development in zebrafish. Preliminary work described in this proposal shows that these genes are required for development of the mammalian head. Lack of Chd in an inbred genetic background results in a group of craniofacial skeletal and soft-tissue defects involving neural crest derivatives, similar to those seen in certain human syndromes. Chd and Nog together are required early for head development, but are also involved specifically in development of the forebrain, mouth, nose, mandible, numerous bones of the skull, and other craniofacial tissues. The major aims of this proposal are: 1) to characterize the spatiotemporal expression patterns of Chd and Nog to clarify their roles in craniofacial development; 2) to determine the critical sites and times of action for Chd and Nog in head induction using embryonic stem cell chimeras and tissue recombinants; 3) to determine the functions of these genes in growth and patterning of craniofacial tissues; and 4) to assess whether ectopic BMP signaling reproduces the craniofacial defects of the mutants.