Cell Biological Determinants of Jaw Size

下巴大小的细胞生物学决定因素

• 批准号: 8126101
• 负责人: Jennifer Leslie Fish
• 金额: $ 5.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-07 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8126101
• 关键词: Affect; Apoptosis; Automobile Driving; Beak; Biochemical; Biological; Birds; Branchial arch structure; Breathing; Cartilage; Cell Count; Cell Death; Cells; Cessation of life; Child; Congenital Abnormality; Connective Tissue; Death Rate; Defect; Deformity; Development; Developmental Process; Diet; Disease; Down Syndrome; Ducks; Environment; Exhibits; Genetic; Goals; Habits; Individual; Injury; Jaw; Length; Link; Mandible; Mandibulofacial Dysostosis; Micrognathism; Modeling; Molecular; Motor Skills; Mus; Muscle; Natural regeneration; Neural Crest; Neural Crest Cell; Neural Fold; Neuroepithelial; Operative Surgical Procedures; Pattern; Population; Prevention; Process; Proliferating; Quail; Regulation; Risk; Robin bird; Role; Seeds; Shapes; Skeleton; Specific qualifier value; Survival Rate; System; Testing; Tissues; Transplantation; Variant; airway obstruction; base; bone; craniofacial; feeding; migration; neural plate; oral motor; prevent; progenitor; programs; relating to nervous system; repaired; skeletal; tooth crowding; treatment effect

DESCRIPTION (provided by applicant): Proper establishment of jaw length is essential to feeding, breathing, and normal development of oral-motor skills. Micrognathia, also referred to as mandibular hypoplasia, is a condition where the jaw is undersized. Treatment for craniofacial defects such as micrognathia often involves multiple surgical interventions, a lengthy, costly, and emotionally and physically draining process. Prevention, therefore, provides a welcome alternative for at-risk individuals. Identifying potential strategies for rescue or regeneration depends, however, on an understanding of the developmental processes regulating jaw size. The jaw, along with most of the craniofacial skeleton, derives from the neural crest (NC), which is a transient, multi-potent cell population that arises at the border of the neural plate. The size of jaws may be directly linked to the size of the progenitor population (i.e., number) of NC. At least three parameters are likely to contribute to variation in NC number: the number of cells that are specified as NC precursors (as opposed to neuroepithelial or ectodermal precursors), the rate of NC cell death, and the rate of NC proliferation. In fact, several studies have closely associated micrognathia with a change in NC number as a result of decreased NC proliferation or increased NC death. Our preliminary analyses indicate that species-specific differences in jaw size arise during development and may be associated with differences in NC number. We hypothesize that the number of neural crest cells regulates jaw size and that species-specific differences in jaw size arise from evolutionary changes in the number of NC precursors, the rate of NC survival and/or the rate of NC proliferation. To test our hypothesis, we will manipulate the number of NC precursors, modulate NC cell death, alter NC proliferation, and assess the effect of these treatments on jaw size. Our proposal has three Specific Aims, focusing on the lower jaw skeleton and investigating the role of three parameters likely to contribute to jaw size. Specific Aim 1 will determine if the number of cells specified as NC precursors regulates jaw size. Specific Aim 2 will determine if differences in survival of NC contribute to differences in jaw size. Finally, Specific Aim 3 will determine if proliferation rates of NC regulate jaw size. Results will be analyzed on molecular, cellular, histological and morphological levels. This project is significant because an understanding of developmental mechanisms regulating jaw size will contribute to the establishment of biologically based preventative therapies. PUBLIC HEALTH RELEVANCE: What controls jaw size? Answering this question is important for preventing birth defects, as well as for devising new therapies to repair or regenerate bones affected by injury or disease. The goal of this project is to identify cell biological mechanisms that determine jaw length.

描述（由申请人提供）：正确确定下颌长度对于进食、呼吸和口腔运动技能的正常发展至关重要。小颌畸形，也称为下颌发育不全，是一种下颌尺寸过小的疾病。小颌畸形等颅面缺陷的治疗通常需要多次手术干预，这是一个漫长、昂贵且耗费精力和体力的过程。因此，预防为高危人群提供了一种受欢迎的选择。然而，确定潜在的拯救或再生策略取决于对调节颌骨大小的发育过程的理解。下巴以及大部分颅面骨骼均源自神经嵴 (NC)，神经嵴是一种短暂的、多能的细胞群，出现在神经板的边缘。颌骨的大小可能与 NC 祖细胞群的大小（即数量）直接相关。至少三个参数可能导致 NC 数量的变化：被指定为 NC 前体细胞（与神经上皮或外胚层前体细胞相反）的细胞数量、NC 细胞死亡率和 NC 增殖率。事实上，一些研究已将小颌畸形与 NC 数量的变化密切相关，这是由于 NC 增殖减少或 NC 死亡增加所致。我们的初步分析表明，物种特异性的下颌尺寸差异在发育过程中出现，并且可能与 NC 数量的差异有关。我们假设神经嵴细胞的数量调节颌骨大小，并且颌骨大小的物种特异性差异源于 NC 前体数量、NC 存活率和/或 NC 增殖率的进化变化。为了检验我们的假设，我们将操纵 NC 前体的数量，调节 NC 细胞死亡，改变 NC 增殖，并评估这些治疗对颌骨大小的影响。我们的提案有三个具体目标，重点关注下颌骨骼并研究可能影响下颌尺寸的三个参数的作用。具体目标 1 将确定指定为 NC 前体的细胞数量是否调节下巴大小。具体目标 2 将确定 NC 存活率的差异是否会导致下颌尺寸的差异。最后，具体目标 3 将确定 NC 的增殖率是否调节颌骨大小。结果将在分子、细胞、组织学和形态学水平上进行分析。该项目意义重大，因为了解调节颌骨大小的发育机制将有助于建立基于生物学的预防疗法。 公共卫生相关性：什么控制下颌尺寸？回答这个问题对于预防出生缺陷以及设计新疗法来修复或再生受损伤或疾病影响的骨骼非常重要。该项目的目标是确定决定下颌长度的细胞生物学机制。