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）：适当地建立下颌长度对于口服运动技能的喂养，呼吸和正常发展至关重要。微处理，也称为下颌骨发育不全，是下颌尺寸不足的情况。颅面缺陷（例如微处理）的治疗通常涉及多种手术干预措施，这是一种漫长，昂贵且在情感和身体上排出的过程。因此，预防为处于危险的人提供了一种可喜的替代方法。但是，确定救援或再生的潜在策略取决于对调节颌骨大小的发展过程的理解。下颌以及大多数颅面骨骼，源自神经rest（NC），这是一种瞬时的，多功能的细胞群，是在神经板的边界上产生的。颌骨的大小可能直接与NC的祖先种群（即数字）的大小有关。至少三个参数可能导致NC数的变化：指定为NC前体的细胞数（与神经上皮或外胚层前体相反），NC细胞死亡率和NC增殖速率。实际上，由于NC增殖降低或NC死亡增加，几项研究与NC数的变化密切相关。我们的初步分析表明，在发育过程中会出现颌骨大小的特定物种差异，并且可能与NC数量的差异有关。我们假设神经rest细胞的数量调节颌骨大小，而颌骨大小的物种特异性差异来自NC前体数量的进化变化，NC存活率和/或NC增殖的速率。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，并评估这些处理对颌骨大小的影响。我们的建议具有三个特定的目标，重点是下颌骨骼，并研究了可能导致下颌大小的三个参数的作用。特定的目标1将确定指定为NC前体的细胞数是否调节下颌大小。特定的目标2将确定NC存活的差异是否导致下颌大小的差异。最后，特定的目标3将确定NC的增殖速率是否调节颌骨的大小。结果将对分子，细胞，组织学和形态学水平进行分析。该项目之所以重要，是因为对调节颌骨大小的发展机制的理解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？回答这个问题对于防止先天缺陷以及设计新疗法以修复或再生受伤或疾病影响的骨骼很重要。该项目的目的是确定确定颌骨长度的细胞生物学机制。