Regulation of craniofacial development by the Dix genes.

描述（由申请人提供）：在最常见和使人衰弱的人类出生缺陷中，有影响颅面组织的缺陷。 在过去的十年中，已经鉴定出了许多在颅面原基中以区域限制模式表达的候选调控基因。 其中包括包括D1x基因家族的同源框转录因子。 在哺乳动物中有三个A型D1x基因（2，3，5）和三个B型D1x基因（1，6，7）。 这些基因在鳃弓原基以及嗅觉器官和耳器官中以嵌套模式表达。 我们已经在小鼠中进行了D1x1，D1x2，D1x1&2和D15的功能缺失突变，并发现这些基因对于颌骨和牙齿以及鼻和耳囊的正常骨骼形态发生是必需的。 D1x的突变体中看到的形态缺陷的D1x的表达模式的比较表明，有一个D1x的组合代码，指定区域的鳃弓和嗅觉和耳器的形态发生。 为了评估我们的D1x功能的组合模型，我们正在研究D1x复合突变体的颅面分子和组织模式。 此外，我们将研究D1x基因调控颅面发育的细胞和分子机制。

DESCRIPTION (provided by applicant): Among the most common and debilitating human birth defects are those that affect craniofacial tissues. The last decade has witnessed the identification of numerous candidate regulatory genes that are expressed in regionally restricted patterns in the craniofacial primordia. Among these are homeobox transcription factors that include the D1x gene family. In mammals there are three Type A D1x genes (2,3,5) and three Type B D1x genes (1,6,7). These genes are expressed in nested patterns in the primordia of the branchial arches as well as the olfactory and otic apparati. We have made loss-of-function mutations of D1x1, D1x2, D1x1&2 and D15 in the mouse and found that these genes are essential for normal skeletal morphogenesis of the jaw apparatus and teeth, as well as the nasal and otic capsules. Comparison of the D1x-expression patterns with the morphological defects seen in the D1x mutants suggests that there is a D1x combinatorial code that specifies regional morphogenesis of the branchial arches and olfactory and otic apparati. To evaluate our combinatorial model of D1x function, we are studying craniofacial molecular and tissue patterning in D1x compound mutants. In addition, we will study the cellular and molecular mechanisms through which the D1x genes regulate craniofacial development.