R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development.
R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development.
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DOI：
10.3390/jdb9030031
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发表时间：
2021-08-12
影响因子：
2.7
通讯作者：
Jeong J
中科院分区：
文献类型：
--
作者：
Dasgupta K;Cesario JM;Ha S;Asam K;Deacon LJ;Song AH;Kim J;Cobb J;Yoon JK;Jeong J
牙齿的发育需要间充质和上皮之间由多种途径介导的复杂信号相互作用。例如，经典的WNT信号传导对于牙齿发生的许多方面都至关重要，抑制该途径会在早期阶段阻止牙齿发育。R-spondins（RSPO）是一种分泌蛋白，它们主要增强WNT信号传导。虽然RSPO已被证明在许多器官的发育中发挥重要作用，但它们在牙齿发育中的作用尚不清楚。先前的一项研究报告说，老鼠的Rspo 2突变导致了多余的下臼齿，而在正常位置形成的牙齿没有明显的异常。因为多个Rspo基因在口面区域表达，所以Rspo 2突变体的相对温和的表型可能是由于其他RSPO蛋白的功能补偿。我们发现，在颅面间充质中失活Rspo 3导致下切牙的损失，这并没有超过芽阶段的进展。Rspo 2和Rspo 3的同时缺失导致早期颅面发育严重中断，并伴随着所有牙齿的发育受损。总之，这些结果表明Rspo 3是哺乳动物牙齿和颅面发育的重要调节因子。
Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development.
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