Cloning/characterization of novel downstream targets & expression/functional analysis of Hoxa2

同源异型盒蛋白是形态发生过程的强有力的调节剂，也是发育过程中前后轴的重要决定因素。 同源异型盒基因家族的成员主要通过存在60个氨基酸的DNA结合区域（同源异型域）来识别。同源结构域具有螺旋-转角-螺旋基序，其结合DNA中的特定核苷酸序列，从而增强或抑制相应靶基因的表达。我的研究计划的长期目标是通过染色质免疫沉淀（ChIP）来表征在我的实验室中分离的新的Hoxa 2下游靶基因（Tasp和Dyrk 4）的功能。特别是，我们的重点是确定他们在视觉系统和腭发育中与Hoxa 2一起发挥什么样的功能作用。本研究的具体目标是：1。表征Hoxa 2下游靶标的体内和体外结合特异性; 2. Hoxa 2及其下游靶标在神经视网膜中的功能分析;和3.识别Hoxa 2-/-小鼠腭裂发育的相关机制。对Hoxa 2及其下游靶点的功能性研究将有助于阐明Hoxa 2在多胚层中介导神经视网膜分化和腭发育的机制。这项研究将促进我们对Hoxa 2在正常视力和腭裂形成（一种常见的人类出生缺陷）中的作用的理解。

Homeobox proteins are powerful regulators of morphogenetic processes and important determinants of the anterior-posterior axis during development.  Members of the homeobox gene family are primarily recognized by the presence of a 60 amino acid DNA binding region, the homeodomain. The homeodomain has a helix-turn-helix motif that binds to specific nucleotide sequences in DNA thereby enhancing or suppressing the expression of the corresponding target genes. The long-term goal of my research program is to characterize the function of new Hoxa2 downstream target genes (Tasp and Dyrk4) isolated in my lab by chromatin immunoprecipitation (ChIP). In particular, our focus is to identify what functional role they play in concert with Hoxa2 in the visual system and in palatogenesis. The specific aims of the present proposed research are: 1. Characterize in vivo and in vitro binding specificity of Hoxa2 downstream targets; 2. Functional analysis of Hoxa2 and its downstream targets in the neural retina; and 3. Identify mechanism(s) involved in cleft palate development in Hoxa2-/-mice. Characterizing the functional role of Hoxa2 and its the downstream targets will decipher the mechanism(s) that allow Hoxa2 to act in multiple germ layers to mediate neural retina differentiation and palatogenesis. This research will advance our understanding of the role of Hoxa2 in normal vision and in cleft palate formation (a common human birth defect).