Prickle1 regulates differentiation of frontal bone osteoblasts.
Prickle1 regulates differentiation of frontal bone osteoblasts.
复制标题
Prickle1 调节额骨成骨细胞的分化。
DOI：
10.1038/s41598-018-36742-0
复制
发表时间：
2018
影响因子：
4.6
通讯作者：
Szabo-Rogers,HeatherL
中科院分区：
文献类型：
--
作者：
Wan,Yong;Lantz,Brandi;Cusack,BrianJ;Szabo-Rogers,HeatherL
扩大的囟门和较小的额骨导致颅骨机械受损。这两种表型都可以从颅骨原基中成骨细胞的迁移和分化缺陷发展而来。Wnt/Planar cell polarity（Wnt/PCP）信号通路调节其他组织中的细胞迁移和运动，并使我们测试了Wnt/PCP通路的核心组分Prickle 1在颅骨中的作用。在这些研究中，我们使用了名为Prickle 1Beetlejuice（Prickle 1Bj）的Prickle 1错义等位基因。Prickle 1Bj/Bj突变体为小头畸形，额骨发育不全，额骨之间的囟增大，而顶骨正常。Prickle 1Bj/Bj突变体还有其他几种颅面缺陷，包括中线唇裂、不完全渗透性腭裂和头部近端-远端生长减少。我们观察到在Prickle 1Bj/Bj突变体的额骨致密化中Wnt/β-catenin和Hedgehog信号减少。令人惊讶的是，较小的额骨并不是由细胞增殖或死亡缺陷引起的，而是额骨成骨细胞前体中显著延迟的分化和迁移标志物表达降低。我们的数据表明，Prickle 1蛋白功能有助于额骨成骨细胞前体的迁移和分化。
Enlarged fontanelles and smaller frontal bones result in a mechanically compromised skull. Both phenotypes could develop from defective migration and differentiation of osteoblasts in the skull bone primordia. The Wnt/Planar cell polarity (Wnt/PCP) signaling pathway regulates cell migration and movement in other tissues and led us to test the role ofPrickle1, a core component of the Wnt/PCP pathway, in the skull. For these studies, we used the missense allele ofPrickle1namedPrickle1Beetlejuice(Prickle1Bj). ThePrickle1Bj/Bjmutants are microcephalic and develop enlarged fontanelles between insufficient frontal bones, while the parietal bones are normal.Prickle1Bj/Bjmutants have several other craniofacial defects including a midline cleft lip, incompletely penetrant cleft palate, and decreased proximal-distal growth of the head. We observed decreased Wnt/β-catenin and Hedgehog signaling in the frontal bone condensations of thePrickle1Bj/Bjmutants. Surprisingly, the smaller frontal bones do not result from defects in cell proliferation or death, but rather significantly delayed differentiation and decreased expression of migratory markers in the frontal bone osteoblast precursors. Our data suggests thatPrickle1protein function contributes to both the migration and differentiation of osteoblast precursors in the frontal bone.