Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration

Abstract

The healing of bone often involves a cartilage intermediate, yet how such cartilage is induced and utilized during repair is not fully understood. By studying a model of large-scale bone regeneration in the lower jaw of adult zebrafish, we show that chondrocytes are crucial for generating thick bone during repair. During jawbone regeneration, we find that chondrocytes co-express genes associated with osteoblast differentiation and produce extensive mineralization, which is in marked contrast to the behavior of chondrocytes during facial skeletal development. We also identify the likely source of repair chondrocytes as a population of Runx2− cells that emanate from the periosteum, a tissue that normally contributes only osteoblasts during homeostasis. Analysis of Indian hedgehog homolog a (ihha) mutants shows that the ability of periosteal cells to generate cartilage in response to injury depends on a repair-specific role of Ihha in the induction as opposed to the proliferation of chondrocytes. The largescale regeneration of the zebrafish jawbone thus employs a cartilage differentiation program distinct from that seen during development, with the bone-forming potential of repair chondrocytes potentially due to their derivation from osteogenic cells in the periosteum.

Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools

“…We did not address whether these cells represent a single cartilage-forming population or a mixture of committed cell types that are poised to contribute to cartilage and later stages of bone formation that were not visualized in these experiments. In some regenerative contexts, cells retain a dual identity, displaying aspects of both osteo- and chondroprogenitors (Paul et al., 2016). …”

Distinct requirements of wls , wnt9a , wnt5b and gpc4 in regulating chondrocyte maturation and timing of endochondral ossification

“…Compared with mammals, endochondral bone formation ( e.g. ceratohyal) occurs first by differentiation of perichondral cells into osteoblasts that then forms a shell of bony mineralization (Eames et al, 2012; Hammond and Schulte-Merker, 2009; Jing et al, 2015; Paul et al, 2016). Here, we highlight the role of the non-canonical Wnt signaling pathway in temporal regulation of the endochondral ossification process.…”

“…Cranial neural crest cells (NCC) are assembled into cartilaginous structures that prefigure development of the craniofacial skeleton (Eames et al, 2012; Hammond and Schulte-Merker, 2009; Kague et al, 2012; Olsen et al, 2000; Paul et al, 2016). After migrating into the first (mandibular) and second (hyoid) pharyngeal arches, CNCCs give rise to a series of cartilaginous anlage (Mork and Crump, 2015).…”

“…In zebrafish, the mentomeckelian (distal midline) and retroarticulars (proximal jaw joint) form through endochondral ossification while the dentary bone (body) form through intramembranous ossification (Eames et al, 2013). Other craniofacial bones that undergo endochondral ossification include the ceratohyal and the ceratobranchials (Hammond and Schulte-Merker, 2009; Paul et al, 2016; Schilling and Kimmel, 1994, 1997). …”

Tissue regeneration during lower jaw restoration in zebrafish shows some features of epimorphic regeneration

“…Lower jaw regeneration has been reported in newts and in zebrafish (Ferretti, ; Ghosh, Thorogood, & Ferretti, ; Goss & Stagg, ; Kurosaka, Takano‐Yamamoto, Yamashiro, & Agata, ; Paul et al., ; Wang et al., ; Zhang et al., ). In particular, newts in the larval stage fully regenerate the lower jaw and restore the structure completely.…”