Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors

Abstract

The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

A tale of two cities: The genetic mechanisms governing calvarial bone development

“…Thus SRY‐box 9 (Sox9), the key determinant of cartilage formation which is required in endochondral ossification, is dispensable for intramembranous skull bone formation (Bi, Deng, Zhang, Behringer, & De Crombrugghe, ; Mori‐Akiyama, Akiyama, Rowitch, & de Crombrugghe, ). Third, the skull bones must differentiate and ossify in a unique environment within close proximity to other CNCC‐ and PM‐ derived tissues such as the dermis, meninges, sutures, and muscle (Goodnough et al, ; Kasner et al, ; Michailovici, Eigler, & Tzahor, ; Tran et al, ). The simultaneous differentiation of tissues within close proximity to one another poses developmental and genetic constraints for establishing the calvarial bone progenitors.…”

Molecular control of nitric oxide synthesis through eNOS and caveolin-1 interaction regulates osteogenic differentiation of adipose-derived stem cells by modulation of Wnt/β-catenin signaling

“…The osteoblast differentiation program of MSCs is switched on by cell recruitment, and timely expression of genes including Runx2, alkaline phosphatase (ALP), type I collagen (ColA1), and osteocalcin (OC) followed by extracellular matrix mineralization [12]. This process can be induced by soluble molecules such as bone morphogenetic proteins (BMPs) [13] or Wnts [14–16] that activate several pathways and other various downstream signals such as protein kinase [17] and growth factors [18] to trigger osteoblast differentiation of mesenchymal stem cells.…”

Twist1 contributes to cranial bone initiation and dermal condensation by maintaining wnt signaling responsiveness

“…A,B) and in the supraorbital arch mesenchyme using Twist2Cre/Dermo1Cre (Fig. B,D) between E10.5 and E12.5 (Yu, ; Carpenter et al, ; Tran et al, ; Reid et al, ; Goodnough et al, ). Twist1 protein was expressed in the cranial mesenchyme containing cranial bone and dermal progenitors at E12.5 in the Crect/+; Wls fl/+ controls.…”

“…Therefore, we tested if the conditional Twist1 mutants have altered expression of Wnt signaling pathway components and transduction in vivo. Wnt16, a canonical Wnt signaling pathway ligand, is expressed in cranial bone progenitors during cranial bone lineage commitment and is involved in intramembranous ossification of skull bones (Goodnough et al, ; Jiang et al, ). Wnt16 protein was expressed in the osteoid of the developing frontal bone in the controls at E13.5 and was either diminished or retarded in Twist1 mutants (Fig.…”