GATA3 is essential for separating patterning domains during facial morphogenesis
GATA3 is essential for separating patterning domains during facial morphogenesis
复制标题
DOI：
10.1242/dev.199534
复制
发表时间：
2021-09-01
期刊：
影响因子：
4.6
通讯作者：
Clouthier, David E.
中科院分区：
文献类型：
--
作者：
Abe, Makoto;Cox, Timothy C.;Clouthier, David E.
第一咽弓的下颌骨和上颌骨内的神经嵴细胞（NCC）最初能够对来自任何一个区域的信号做出反应。然而，仅部分理解的机制建立发育组织边界，以确保空间正确的图案。在面部发育的“铰链和帽”模型中，来自两个腹侧相邻组织（帽）的信号图案化相邻组织，而被称为上下颌接合部（铰链）的中间区域保持下颌和上颌域的分离。一个帽信号是GATA 3，其是锌指转录因子的加塔家族的成员，在第一牙弓的下颌和上颌部分的最腹侧部分中具有独特的表达模式。我们发现小鼠胚胎中Gata3的破坏会导致颅面矮小症和颏畸形骨融合（上下颌骨融合）的研究，这是由上下颌交界处附近的NCC内BMP 4和FGF 8基因调控网络的变化引起的。因此，GATA 3是建立在发育过程中功能性分离上颌骨和下颌的因素网络的关键组成部分。
Neural crest cells (NCCs) within the mandibular and maxillary prominences of the first pharyngeal arch are initially competent to respond to signals from either region. However, mechanisms that are only partially understood establish developmental tissue boundaries to ensure spatially correct patterning. In the 'hinge and caps' model of facial development, signals from both ventral prominences (the caps) pattern the adjacent tissues whereas the intervening region, referred to as the maxillomandibular junction (the hinge), maintains separation of the mandibular and maxillary domains. One cap signal is GATA3, a member of the GATA family of zinc-finger transcription factors with a distinct expression pattern in the ventral-most part of the mandibular and maxillary portions of the first arch. Here, we show that disruption of Gata3 in mouse embryos leads to craniofacial microsomia and syngnathia (bony fusion of the upper and lower jaws) that results from changes in BMP4 and FGF8 gene regulatory networks within NCCs near the maxillomandibular junction. GATA3 is thus a crucial component in establishing the network of factors that functionally separate the upper and lower jaws during development.