Mechanisms of digit patterning and evolution

描述(由申请人提供)： 四足动物肢体骨架的全球前后极性由Sonic Hedgehog信号控制，但下游分子和发育机制控制数字识别和数字数量以及形态变异仍然知之甚少。T-box转录因子家族的五个成员已经被鉴定出来，它们表现出与在发育中的雏鸡肢体中指定数字身份的角色一致的空间和时间表达模式。这项建议旨在通过鸡模型系统中的功能增益错误表达研究来测试T-box基因在调节数字模式中的功能作用，并通过在基础四足类(Ambystoma)和放线翅目(Lesssteus)分类群中的比较表达和功能分析来评估T-box功能的保守性。为了深入了解数字减少的进化机制，我们将建立一个基于DNA序列同源性的系统发育树，以显示出四足动物肢体减少的最多样化的频谱。在这个DNA序列系统发展的背景下对数字模式的比较将提供在密切相关的自然种群中肢体减少的实际进化过程的第一个例子。

DESCRIPTION (provided by applicant): Global anteroposterior polarity of the tetrapod limb skeleton is controlled by Sonic hedgehog signaling, but downstream molecular and developmental mechanisms controlling digit identity and digit number, and morphological variation, remain poorly understood. Five members of the T-box family of transcription factors have been identified that exhibit spatial and temporal expression patterns consistent with a role in specifying digit identity in the developing chick limb. This proposal is designed to test the functional roles of T-box genes in regulating digit patterning through gain-of-function misexpression studies in the chick model system, and to assess the conservation of T-box function through comparative expression and function analyses in basal tetrapod (Ambystoma) and actinopterygian (Lepisosteus) taxa. To gain insight into the evolutionary mechanisms of digit reduction, a phylogenetic tree based on DNA sequence homology will be generated for the scincid lizard genus Lerista, which exhibits the most diverse spectrum of tetrapod limb reduction. Comparison of digital patterns within the context of this DNA sequence phylogeny will provide the first example of an actual evolutionary progression of limb reduction in a closely related, natural population.