Regulation of craniofacial development by the Dix genes.

在最常见的和使人衰弱的人类出生缺陷中，有影响颅面组织的缺陷。过去十年中，已经鉴定出了许多候选调节基因，这些基因在颅面原基中以区域限制的模式表达。在这些基因中，有包括Dlx基因家族的同源框转录因子。在哺乳动物中，有三种A型Dlx基因（2，3，5）和三个B型Dlx基因（1，6，7）。这些基因在鳃弓的原基以及嗅觉和耳器官中以巢状模式表达。我们已经在小鼠中使Dlx 1、Dlx 2、Dlx 1&2和Dlx 5丧失功能突变，并发现这些基因对于颌器官和牙齿的正常骨骼形态发生是必需的，以及鼻和耳囊Dlx表达模式与Dlx突变体中所见的形态学缺陷的比较表明，存在Dlx组合密码，其指定鳃弓和嗅觉和耳器官的区域形态发生。为了评估我们的Dlx功能的组合模型，我们正在研究Dlx复合突变体中的颅面分子和组织模式。此外，我们将研究Dlx基因调控唇面发育的细胞和分子机制。

EXCEED THE SPACE PROVIDED 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 Dlx gene family In mammals there are three Type A Dlx genes (2,3,5) and three Type B Dlx 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 appatati We have made loss-of-function mutations of Dlxl, Dlx2, Dlxl&2 and Dlx5 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 Dlx-expression patterns with the morphological defects seen in the Dlx mutants suggests that there is a Dlx combinatorial code that specifies regional morphogenesis of the branchial arches and olfactory and otic apparati To evaluate our combinatorial model of Dlx function, we are studying craniofacial molecular and tissue patterning in Dlx compound mutants In addition, we will study the cellular and molecular mechanisms through which the Dlx genes regulate claniofacial development PERFORMANCE SITE ========================================Section End===========================================