神经嵴（NC）由干细胞构成，位于神经管的边缘，能够分化成为多种类型细胞。NC发育异常会导致出生缺陷等人类疾病综合症，如颅面发生异常。NC的发育受到多种调控机制，其中表观修饰是研究热点。Brca1/2是抑癌基因，在胚胎发育中具有重要作用。BRCA1/2参与调控细胞周期、转录与DNA损伤修复，维持基因组稳定和表观修饰。目前，关于BRCA1/2在神经嵴发育中的作用未见报道。本研究在小鼠NC细胞中条件性敲除Brca1/2基因，探讨BRCA1/2在NC发育中的作用及机制，并比较BRCA1和BRCA2的功能差异。前期研究表明Brca1/2缺陷小鼠颅面发生异常，引起NC发育不同时期的基因表达失调，包括NC谱系决定，MSC谱系决定及成骨发生等。我们认为BRCA1/2参与基因组水平或表观修饰调控神经嵴的发育。通过本研究可以挖掘抑癌基因在NC发育过程中可能的调控机制，对发育生物学及肿瘤研究尤为重要。

Neural crest (NC) cells are a transient population of stem-cells that arise from neuroepithelial precursors during early embryonic development to generate a wide spectrum of derivatives. Cranial NC cells arise between the posterior fore brain and posterior hindbrain and migrate into the facial primordial to generate the vast majority of the vertebrate head, including the cranial ganglia, connective tissue, tendons, osteoblasts, chondrocytes and melanocytes. Many of the most common human birth defects are related to abnormal neural crest development. Cranial NC malformation can lead to craniofacial defects like cleft lip and palate. Specific cell fates of CNCCs are controlled by positional cues that determine intrinsic gene expression patterns that are partially specified already at emigration from the neural tube. There is growing evidence to support roles for epigenetic regulation as critical for many aspects of neural crest development, including of DNA methylation, histone methylation, histone acetylation and Polycomb repressive complex. Breast cancer susceptibility gene1/2 (BRCA1/2) was identified as a hereditary cancer susceptibility gene which increased risk for the development of breast and ovarian cancer in Brca1/2 mutation carriers. BRCA1/2 also play an important role in embryogenesis, neurogenesis and hair follicle development. To date, a large number of biochemical activities have been linked to BRCA1 function, which include DNA damage response and repair, transcription regulation, chromatin remodeling, heterochromatin maintenance, among others. However, how BRCA1/2 regulates cell differentiation and how BRCA1/2 deregulation contributes to development of neural crest cells remain elusive. In present study, we examined the role of BRCA1/2 in NC development by conditionally ablating BRCA1/2 in premigratory NCCs in vivo. Interestingly, Brca1/2 deficiency derepressed neural crest markers Foxd3 and Sox10, and deregulates the MSCs lineage and osteogenesis markers, such as Dlx5 and Runx2, resulting in defect of craniofacial morphogenesis. Thus, we hypothesis that loss of BRCA1/2 in NCC perturb the NCC specification and terminal differentiation of downstream by epigenetic control. Meanwhile, the difference function of BRCA1 and BRCA2 in NC development will be investigated. Understanding specific role of BRCA1/2 in neural crest development is of great interest and importance to both developmental biology and tumourgenesis.