Molecular ontogeny of the skeleton

Abstract

From a traditional viewpoint, skeletal elements form by two distinct processes: endochondral ossification, during which a cartilage template is replaced by bone, and intramembranous ossification, whereby mesenchymal cells differentiate directly into osteoblasts. There are inherent difficulties with this historical classification scheme, not the least of which is that bones typically described as endochondral actually form bone through an intramembranous process, and that some membranous bones may have a transient chondrogenic phase. These innate contradictions can be circumvented if molecular and cellular, rather than histogenic, criteria are used to describe the process of skeletal tissue formation. Within the past decade, clinical examinations of human skeletal syndromes have led to the identification and subsequent characterization of regulatory molecules that direct chondrogenesis and osteogenesis in every skeletal element of the body. In this review, we survey these molecules and the tissue interactions that may regulate their expression. What emerges is a new paradigm, by which we can explain and understand the process of normal- and abnormal-skeletal development.

Characterization of two new zebrafish members of the hedgehog family: Atypical expression of a zebrafish indian hedgehog gene in skeletal elements of both endochondral and dermal origins

“…We did not detect expression of ihha in forming intramembranous bones of the craniofacial region, which is consistent with previous studies that showed that intramembranous bones do form in ihh Ϫ/Ϫ mouse, although their growth is impaired by the mutation (StJacques et al, 1999). Contrarily to the cell-type restricted expression of ihha, col10a1-expressing cells seem to belong to distinct populations: First, col10a1 is expressed in hypertrophic chondrocytes, as described in previous studies of cartilage development (Eames et al, 2003;Tchetina et al, 2003;Shen, 2005). Second, col10a1 is expressed in flat cells at two different locations: First, we observed col10a1 in flat cells that may correspond to osteoblasts of the forming cranial intramembranous bones (operculum, parasphenoid, and ectopterygoid) and pectoral fin girdle (cleithrum).…”

“…Endochondral ossification gives rise to most of the axial and appendicular skeletal elements, and is initiated by the formation of a cartilage precursor that is used as a model for subsequent ossification (Hall and Miyake, 2000;Olsen et al, 2000). During maturation of cartilage, chondrocytes first stop proliferating and progressively differentiate into hypertrophic chondrocytes (St-Jacques et al, 1999;Karp et al, 2000;Eames et al, 2003). This transition is characterized by the expression of Ihh (Bitgood and McMahon, 1995;Vortkamp et al, 1996), a significant increase in cell size, and the expression of new extracellular matrix components, including Collagen type X (Col10a1) in hypertrophic chondrocytes (Pathi et al, 2001;Tchetina et al, 2003;Yan et al, 2005).…”

Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues

“…During intramembranous ossification (reviewed in Eames and colleagues (1) and Karsenty and colleagues (2) ), signals from epithelia adjacent to the condensations induce the expression of Runx2, which promotes osteoblast differentiation and directly upregulates osteogenic genes like Osterix/Sp7 (Osx), Collagen I, and Osteocalcin/Bglap (Osc). (3)(4)(5)(6)(7)(8) With ongoing maturation, osteoblasts synthesize high amounts of extracellular matrix mainly composed of Collagen I and proteoglycans.…”

A hierarchy of Runx transcription factors modulate the onset of chondrogenesis in craniofacial endochondral bones in zebrafish

“…The vertebrate skeleton is made up principally of three structural tissues: bone, replacement cartilage, and permanent cartilage (Eames et al, 2003). All three are derived from mesenchymal cell condensations that form skeletogenic fields of osteochondroprogenitor cells (Hall and Miyake, 2000).…”