The Roles of BMP Genes and Morphogenesis of the Appendicular and Dermal Skeletons

BMP 基因的作用以及阑尾和真皮骨骼的形态发生

• 批准号: 7432430
• 负责人: CLIFFORD J. TABIN
• 金额: $ 40.38万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7432430
• 关键词: Alleles; BMP2 gene; BMP4; BMP7 gene; Biological Models; Bone Development; Cartilage; Chondrogenesis; Complex; Dermal; Development; Differentiation and Growth; Elements; Embryo; Event; Excision; Family member; Funding; Gene Expression; Genes; Genetic; Growth; Growth Factor; Laboratories; Learning; Limb structure; Mediating; Morphogenesis; Mus; Neural Crest; Osteoblasts; Osteogenesis; Pattern; Pattern Formation; Phenotype; Physical condensation; Play; Process; Protein Family; Proteins; Regulation; Retroviral Vector; Role; Screening procedure; Signal Transduction; Signaling Molecule; Skeletal Development; Skeletal system; Skeleton; Staging; System; Viral; Work; bone; bone morphogenic protein; cell type; craniofacial; insight; interest; loss of function; novel; progenitor; promoter; recombinase; research study

Secreted proteins direct the initiation, growth and patterning or the developing skeletal elements. BMPs are important examples of such factors. BMP family members were first identified over 15 years ago by their ability to induce bone in experimental settings. Yet surprisingly little has been learned about the precise roles different members of this family play during normal chondrogenesis and osteogenesis. This is a complex problem, as there is likely to be significant functional redundancy between different BMP family members. BMPs are likely to play multiple roles at distinct steps of skeletal formation making later stages harder to assess and moreover, loss of function of several of these BMP genes results in early embryonic lethality before skeletal phenotypes can be assessed.. We will take a genetic approach to this problem in mice, utilizing conditional alleles of BMP2 and BMP4 and a null allele of BMP7. Function of thse genes will be removed, singly and in combination, by expressing ere recombinase from promoters known to drive expression at various steps of skeletal formation. In particular, we will utilize an existing Prx1::cre line to remove BMP activity prior to chondrogenesis in the limb, and Coll:: ere to remove their activity in osteoblasts within the appendicular skeleton. Similarly, these gene activities will be removed in the neural crest-derived craniofacial skeletal progenitors with a Wntl::cre and Col::cre will again be used to study the roles of BMPs in dermal bone formation. The cellular events of dermal bone formation are very poorly understood. We will use the chick system to identify markers for different intermediate cell types during dermal ossification, determine when and where growth factors are expressed, and use viral misexpression in chick to study their roles in regulating dermal bone formation.

分泌的蛋白质指导骨骼元素的形成、生长和形成模式。