Cell Biological Determinants of Jaw Size

下巴大小的细胞生物学决定因素

• 批准号: 8261053
• 负责人: Jennifer Leslie Fish
• 金额: $ 5.65万
• 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/8261053
• 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; public health relevance; 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)：适当的颌骨长度对进食、呼吸和口腔运动技能的正常发展是必不可少的。小颌症，也被称为下颌发育不全，是一种颌骨过小的情况。小下颌畸形等头面部缺陷的治疗通常需要多个手术干预，这是一个漫长、昂贵、耗费情感和体力的过程。因此，预防为高危个人提供了一个受欢迎的替代方案。然而，确定拯救或再生的潜在策略取决于对调节颌骨大小的发育过程的理解。颌骨和大多数头面部骨骼一起来自神经沟(NC)，它是一个瞬时的、多潜能的细胞群体，出现在神经板的边界。颌骨的大小可能直接与NC的祖细胞种群的大小(即数量)有关。至少有三个参数可能导致NC数量的变化：被指定为NC前体的细胞数量(相对于神经上皮或外胚层前体)、NC细胞死亡率和NC增殖率。事实上，一些研究已经将小下颌畸形与NC数量的变化密切相关，这是NC增殖减少或NC死亡增加的结果。我们的初步分析表明，不同物种在颌骨大小上的差异出现在发育过程中，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的大小，并且颌骨大小的物种差异源于NC前体细胞的数量、NC存活率和/或NC增殖率的进化变化。为了验证我们的假设，我们将操纵NC前体的数量，调节NC细胞的死亡，改变NC的增殖，并评估这些治疗对颌骨大小的影响。我们的建议有三个具体目标，重点是下颌骨骨骼，并调查可能影响颌骨大小的三个参数的作用。具体目标1将确定指定为NC前体的细胞数量是否调节颌骨大小。具体目标2将确定NC存活率的差异是否会导致颌骨大小的差异。最后，特定的目标3将决定NC的增殖率是否调节颌骨的大小。结果将在分子、细胞、组织和形态水平上进行分析。这个项目意义重大，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的预防性治疗。 公共卫生相关性：是什么控制了颌骨的大小？回答这个问题对于预防出生缺陷以及设计修复或再生受伤害或疾病影响的骨骼的新疗法都很重要。该项目的目标是确定决定颌骨长度的细胞生物学机制。