Harvard School of Dental Medicine, Boston, MA, USA.
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
Sci Rep. 2021 Mar 12;11(1):5871. doi: 10.1038/s41598-021-85415-y.
Wnt signaling plays a critical role in craniofacial patterning, as well as tooth and bone development. Rspo2 and Rspo3 are key regulators of Wnt signaling. However, their coordinated function and relative requirement in craniofacial development and odontogensis are poorly understood. We showed that in zebrafish rspo2 and rspo3 are both expressed in osteoprogenitors in the embryonic craniofacial skeleton. This is in contrast to mouse development, where Rspo3 is expressed in osteoprogenitors while Rspo2 expression is not observed. In zebrafish, rspo2 and rspo3 are broadly expressed in the pulp, odontoblasts and epithelial crypts. However, in the developing molars of the mouse, Rspo3 is largely expressed in the dental follicle and alveolar mesenchyme while Rspo2 expression is restricted to the tooth germ. While Rspo3 ablation in the mouse is embryonic lethal, zebrafish rspo3-/- mutants are viable with modest decrease in Meckel's cartilage rostral length. However, compound disruption of rspo3 and rspo2 revealed synergistic roles of these genes in cartilage morphogenesis, fin development, and pharyngeal tooth development. Adult rspo3 zebrafish mutants exhibit a dysmorphic cranial skeleton and decreased average tooth number. This study highlights the differential functions of Rspo2 and Rspo3 in dentocranial morphogenesis in zebrafish and in mouse.
Wnt 信号在颅面模式形成以及牙齿和骨骼发育中起着关键作用。Rspo2 和 Rspo3 是 Wnt 信号的关键调节因子。然而，它们在颅面发育和牙发生中的协调功能和相对需求知之甚少。我们发现，在斑马鱼中，rspo2 和 rspo3 均在胚胎颅面骨骼的成骨细胞前体中表达。这与小鼠的发育形成对比，在小鼠中，Rspo3 在成骨细胞前体中表达，而 Rspo2 表达则观察不到。在斑马鱼中，rspo2 和 rspo3 在牙髓、成牙本质细胞和上皮隐窝中广泛表达。然而，在小鼠发育中的磨牙中，Rspo3 主要在牙囊和牙槽间质中表达，而 Rspo2 表达则局限于牙胚。虽然 Rspo3 在小鼠中的缺失是胚胎致死性的，但斑马鱼 rspo3-/- 突变体是存活的， Meckel 软骨的长度略缩短。然而，rspo3 和 rspo2 的复合缺失揭示了这些基因在软骨形态发生、鳍发育和咽齿发育中的协同作用。成年 rspo3 斑马鱼突变体表现出颅面骨骼畸形和平均牙齿数量减少。本研究强调了 Rspo2 和 Rspo3 在斑马鱼和小鼠 dentocranial 形态发生中的不同功能。
