Prickle1 regulates differentiation of frontal bone osteoblasts

Yong Wan,Brandi Lantz,Brian J Cusack,Heather L Szabo-Rogers

doi:10.1038/s41598-018-36742-0

Abstract

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 of Prickle1, a core component of the Wnt/PCP pathway, in the skull. For these studies, we used the missense allele of Prickle1 named Prickle1Beetlejuice(Prickle1Bj). The Prickle1Bj/Bj mutants are microcephalic and develop enlarged fontanelles between insufficient frontal bones, while the parietal bones are normal. Prickle1Bj/Bj mutants 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 the Prickle1Bj/Bj mutants. 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 that Prickle1 protein function contributes to both the migration and differentiation of osteoblast precursors in the frontal bone.

Highlights

Enlarged fontanelles and smaller frontal bones result in a mechanically compromised skull
We have briefly described the microcephalic phenotype in the Prickle1Bj/Bj mutants previously[20]
We found that the interfrontal suture is enlarged in the Prickle1Bj/Bj mutants while the sagittal suture is unaffected (Fig. 1g)

Summary

Introduction

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 of Prickle[1], a core component of the Wnt/PCP pathway, in the skull. The combined loss of all Wnt ligands in the Wls mutants and the ability of Twist[1] to direct cell movements in the absence of β-catenin imply that both Wnt/PCP and Wnt/β-catenin signaling may be required for apical extension of the frontal bone[13,14]. The Bj mutant mice phenotype is consistent with another independent point mutation of Prickle[1], C251X, including stunted limbs and cleft palate[20,25,26]

Methods

Results

Conclusion