Cartilage and bone of the lower jaw in development and disease

下颌软骨和骨骼的发育和疾病

基本信息

  • 批准号:
    10552606
  • 负责人:
  • 金额:
    $ 76.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-01 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The lower jaw evolved as a structure composed of many bones the largest of which, the dentary, persists as a single lower jawbone in modern mammals, and is referred to as the mandible in humans. Mandibular disorders, often resulting in small jaws, are among the most common human birth defects. These disorders can dramatically affect quality of life, and are often associated, or compound problems with airway obstruction, speech, and feeding. During embryogenesis, development of the mandible is preceded by and associated with a tubular cartilage rod called Meckel's cartilage (MC) and anomalies of MC have been associated with mandibular disorders. Development of MC in modern mammals is complex: the anterior part contributes to the formation of the mandibular symphysis, its posterior part forms cartilages that mineralize endochondrally to form two middle ear bones, and the posterior half of the middle region forms ligaments. Less is known about the anterior half of the middle region of MC, which is transient, present during a small window of embryonic development before it disappears. Established assessments describe MC as a template for the formation of the mandible, but evidence of this is lacking and little is known of the relationship between the midportion of MC and mandibular mineralization, size, and shape or the processes of MC growth in length, perichondrial ossification, and disappearance of MC. We present data demonstrating that MC does not serve as a template in the way cartilaginous models function in endochondral ossification and hypothesize a new role for the mid portion of MC in determining mandibular length, mineralization of the perichondrium, mineralization of the mandible, and its disappearance. Because our findings challenge the traditional role of MC, we have designed this project to validate the developmental events that take place as the midportion of MC disappears and the mandible forms through a detailed analysis of four processes: 1) initiation and growth in length of MC; 2) mineralization of MC perichondrium; 3) mineralization of the mandible; and 4) disappearance of MC. Our approach is based on knowledge we have gained through preliminary investigations of these processes occurring at different times along the length of MC, and spanning the buccal to lingual aspects of the interior of MC. We couple 3D imaging with tissue and cellular analyses of embryonic mutant Sox9flox/flox;Col2a1-CreERT, and Sox9flox/flox mice to precisely define the changing cellular dynamics of the lower jaw in developmental time and anatomical space. These data are used in turn to inform our RNA-seq analyses of the developing MC and mandible directed at recovering the underlying transcriptome by differential gene expression, pathway, and network analyses. We plan cell lineage tracing experiments to determine the fate of cells from the intermediate region of MC, those that initiate MC perichondrial mineralization, and mandible mineralization. Our integrative approach is designed to bring new understanding to lower jaw development and open novel research areas to advance strategies for bone repair, regeneration, and prevention in mandibular disease.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Ethylin Wang Jabs其他文献

Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans
患有黑棘皮病的克鲁宗综合征中的成纤维细胞生长因子受体 3(FGFR3)跨膜突变
  • DOI:
    10.1038/ng1295-462
  • 发表时间:
    1995-12-01
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    Gregory A. Meyers;Seth J. Orlow;Ian R. Munro;Kelly A. Przylepa;Ethylin Wang Jabs
  • 通讯作者:
    Ethylin Wang Jabs
Aural atresia associated with multiple congenital anomalies and mental retardation: A new syndrome
  • DOI:
    10.1016/s0022-3476(87)80017-3
  • 发表时间:
    1987-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Linda F. Cooper;Ethylin Wang Jabs
  • 通讯作者:
    Ethylin Wang Jabs
亚洲人群FOXF2基因多核苷酸多态位点与非综合征型唇腭裂关联的新证据
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bo Zhang;Ethylin Wang Jabs;Alan F. Scott;Terri H. Beaty
  • 通讯作者:
    Terri H. Beaty
国际唇腭裂研究小组数据的基因及基因环境交互作用联合研究关于亚洲人群BMP4基因与非综合征型唇腭裂关联的新证据
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Ethylin Wang Jabs;Margaret M. Parker;Alan F. Scott;Terri H. Beaty
  • 通讯作者:
    Terri H. Beaty
A genome wide screen of Crohn's disease in a large pedigree shows evidence for linkages to chromosomes 11, 16, 8 and 15
  • DOI:
    10.1016/s0016-5085(98)83831-6
  • 发表时间:
    1998-04-15
  • 期刊:
  • 影响因子:
  • 作者:
    Steven R. Brant;Dan Nicolae;Michele C. LaBuda;Romulo Baltazar;Carter Fields;Geoffrey Ravenhill;Mike Pickles;Patrick M. Rohal;Ethylin Wang Jabs;Stephen B. Hanauer;Theodore M. Bayless;Judy H. Cho
  • 通讯作者:
    Judy H. Cho

Ethylin Wang Jabs的其他文献

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{{ truncateString('Ethylin Wang Jabs', 18)}}的其他基金

Cartilage and bone of the lower jaw in development and disease
下颌软骨和骨骼的发育和疾病
  • 批准号:
    10357271
  • 财政年份:
    2022
  • 资助金额:
    $ 76.69万
  • 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
  • 批准号:
    10220643
  • 财政年份:
    2021
  • 资助金额:
    $ 76.69万
  • 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
  • 批准号:
    10663868
  • 财政年份:
    2021
  • 资助金额:
    $ 76.69万
  • 项目类别:
Genetic, Tissue, and Anatomical Interactions in Mandibulofacial Dysmorphogenesis
下颌面部畸形发生中的遗传、组织和解剖学相互作用
  • 批准号:
    10470325
  • 财政年份:
    2021
  • 资助金额:
    $ 76.69万
  • 项目类别:
Transcriptome and Network Analysis of Cleft Palate
腭裂的转录组和网络分析
  • 批准号:
    10539242
  • 财政年份:
    2020
  • 资助金额:
    $ 76.69万
  • 项目类别:
Transcriptome and Network Analysis of Cleft Palate
腭裂的转录组和网络分析
  • 批准号:
    10314049
  • 财政年份:
    2020
  • 资助金额:
    $ 76.69万
  • 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
  • 批准号:
    10159749
  • 财政年份:
    2013
  • 资助金额:
    $ 76.69万
  • 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
  • 批准号:
    9260707
  • 财政年份:
    2013
  • 资助金额:
    $ 76.69万
  • 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
  • 批准号:
    9751946
  • 财政年份:
    2013
  • 资助金额:
    $ 76.69万
  • 项目类别:
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects
系统与发育生物学和出生缺陷的跨学科培训
  • 批准号:
    8640965
  • 财政年份:
    2013
  • 资助金额:
    $ 76.69万
  • 项目类别:

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