Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan.
Development. 2021 Sep 1;148(17). doi: 10.1242/dev.199534. Epub 2021 Sep 7.
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.
神经嵴细胞(NCCs)最初能够在第一咽弓的下颌和上颌突起中响应来自任一区域的信号。然而,部分理解的机制建立了发育组织边界,以确保空间上正确的模式。在面部发育的“铰链和帽”模型中,来自两个腹侧突起(帽)的信号对相邻组织进行了模式化,而中间区域,称为上颌下颌交界处(铰链),则保持了下颌和上颌区域的分离。一个帽信号是 GATA3,它是锌指转录因子家族的 GATA 家族的成员,在第一弓的下颌和上颌部分的最腹侧部分具有独特的表达模式。在这里,我们表明,在小鼠胚胎中破坏 Gata3 会导致颅面骨发育不良和并颌(上下颌骨的骨性融合),这是由于上颌下颌交界处附近的 NCC 中 BMP4 和 FGF8 基因调控网络的变化。因此,GATA3 是在发育过程中建立功能上分离上下颌的因子网络的关键组成部分。