Specification of jaw identity by the Hand2 transcription factor.
Specification of jaw identity by the Hand2 transcription factor.
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DOI：
10.1038/srep28405
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发表时间：
2016-06-22
影响因子：
4.6
通讯作者：
Saga Y
中科院分区：
文献类型：
--
作者：
Funato N;Kokubo H;Nakamura M;Yanagisawa H;Saga Y
下颚（下颌骨）的获得对于有颌脊椎动物在进化上是重要的。在人类中，综合征性颅面畸形往往伴随颌骨异常。基本的螺旋-环-螺旋转录因子Hand 2，这是保守的有颌脊椎动物，是在下颌骨的神经嵴中表达，但不是在上颌过程中的第一鳃弓。在这里，我们提供的证据表明，Hand 2是足够的上颌（上颌骨）到下颌骨的转化，通过调节小鼠同源框转录因子的表达。神经嵴中Hand 2表达的改变将上颌骨转化为具有重复Meckel软骨的下颌骨，这导致了次级腭的缺失。在Hand 2过表达突变体中，非Hox同源框转录因子失调。这些结果表明，手2调节下颌骨发育通过下游基因的手2，因此是一个主要的决定因素颌骨身份。Hand 2可能影响了下颌骨和次级腭的进化获得。
Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel’s cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate.