Centre for Craniofacial & Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences , King's College London, London, SE1 9RT United Kingdom.
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine , Ministry of Education (Hubei-MOST KLOS & KLOBM), School and Hospital of Stomatology, Wuhan University, 430079 Wuhan, China.
Development. 2023 Apr 1;150(7). doi: 10.1242/dev.201464. Epub 2023 Apr 6.
The vestibular lamina (VL) forms the oral vestibule, creating a gap between the teeth, lips and cheeks. In a number of ciliopathies, formation of the vestibule is defective, leading to the creation of multiple frenula. In contrast to the neighbouring dental lamina, which forms the teeth, little is known about the genes that pattern the VL. Here, we establish a molecular signature for the usually non-odontogenic VL in mice and highlight several genes and signalling pathways that may play a role in its development. For one of these, the Sonic hedgehog (Shh) pathway, we show that co-receptors Gas1, Cdon and Boc are highly expressed in the VL and act to enhance the Shh signal from the forming incisor region. In Gas1 mutant mice, expression of Gli1 was disrupted and the VL epithelium failed to extend due to a loss of proliferation. This defect was exacerbated in Boc/Gas1 double mutants and could be phenocopied using cyclopamine in culture. Signals from the forming teeth, therefore, control development of the VL, coordinating the development of the dentition and the oral cavity.
前庭板 (VL) 形成口腔前庭，在牙齿、嘴唇和脸颊之间形成一个间隙。在许多纤毛病中，前庭的形成有缺陷，导致多个系带的形成。与形成牙齿的相邻的牙板不同，人们对塑造 VL 的基因知之甚少。在这里，我们在小鼠中建立了通常非牙源性 VL 的分子特征，并强调了几个可能在其发育中发挥作用的基因和信号通路。对于其中之一，即 Sonic hedgehog (Shh) 通路，我们表明共同受体 Gas1、Cdon 和 Boc 在 VL 中高度表达，并作用于增强来自形成的切牙区域的 Shh 信号。在 Gas1 突变小鼠中，Gli1 的表达被打乱，由于增殖丧失，VL 上皮无法延伸。Boc/Gas1 双突变体中的这种缺陷更为严重，并且可以在培养中使用环巴胺进行表型模拟。因此，来自形成的牙齿的信号控制 VL 的发育，协调牙列和口腔的发育。
