Function and regulation of Lhx genes in craniofacial development

涉及第一鳃弓衍生的颅面异常，包括颌骨、腭部和牙齿，是一种 人类出生缺陷的主要类别。了解颅面部背后的分子遗传学机制 发展对于设计人类疾病的诊断、预防和治疗的创新方法至关重要 缺陷。NIY研究的长期目标是描述调控的转录网络 通过鉴定转录因子和顺式调节元件来发育第一鳃弓 在这一过程中很重要，并决定了层次关系。Lhx6和Lhx3基因，编码 同源结构域转录因子，是第一鳃弓发育的主要调节因子；小鼠突变体 Lhx6和Lhx8缺乏Lhx6和Lhx8的活性，出生时就患有继发性腭裂，没有磨牙。具体来说，我 研究发现，lhx基因对于磨牙和继发性腭部发育的初始步骤是必不可少的。二 关于lhx基因在头面部发育中的功能和调控仍然存在关键问题：1)什么是 牙齿和腭部发育过程中lhx功能的分子和细胞机制？ 2)调控第一鳃中lhx基因表达的上游因子是什么？ 阿奇？我在Roo阶段的研究将使用小鼠突变模型以及 生物化学和分子生物学方法。该项目的成果将提供有关以下方面的重要信息 Lhx6和Lhx8功能和表达的中断如何导致人类头面部缺陷。

Craniofacial abnornialities involving the first branchial arch derivatives, including jaw,,palate, and teeth, are a major class of birth defects in humans. Understanding the molecular genetic mechanisms behind craniofacial development is vital to devising innovative methods for diagnosis, prevention, and treatment of human defects. The long-term goal of niy research is to characterize the transcriptional network that governs development of the first branchial arch, by identifying transcription factors and cis-regulatory elements important in this process, and determining th^eir hierarchic^ relationship. Lhx6 and Lhx3 genes, encoding homeodomain transcription factors, are major regulators of first branchial arch development; mouse mutants lacking the activities of both Lhx6 and Lhx8 are born with cleft secondary palate and no molars. Specifically, I found that the Lhx genes are essential for the initial steps of molar and secondary palate development. Two crucial questions remain on the function and regulation of Lhx genes in craniofacial development: 1) what is the molecular and cellular mechanisms of Lhx function during the initiation of tooth and palate development?, and 2) what are the upstream factprs that regulate the expression of the Lhx genes in the first branchial arch? My research during ROO phase will address these questions using mouse mutant models as well as biochemistry and molecular biology methods. The results of this project will provide critical information on how disruption in Lhx6 and Lhx8 function and expression can contribute to human craniofacial defects.