The Forgotten Skeletogenic Condensations: A Comparison of Early Skeletal Development Amongst Vertebrates

Abstract

The development of a skeletogenic condensation is perhaps the most critical yet considerably overlooked stage of skeletogenesis. Described in this comprehensive review are the mechanisms that facilitate skeletogenic condensation formation, growth, and maintenance to allow for overt differentiation into a skeletal element. This review discusses the current knowledge of gene regulation and characterization of skeletogenic condensations in the chicken, mouse, zebrafish, and other developmental models. We limited our scope to condensations that give rise to the bones and cartilages of the vertebrate skeleton, with a particular focus on craniofacial and limb bud regions. While many of the skeletogenic processes are similar among vertebrate lineages, differences are apparent in the site and timing of the initial epithelial–mesenchymal interactions as well as in whether the condensation has an osteogenic or chondrogenic fate, both within and among species. Further comparative studies are needed to clarify and broaden the existing knowledge of this intricate phenomenon.

In Vitro Fabrication of Hybrid Bone/Cartilage Complex Using Mouse Induced Pluripotent Stem Cells

“…In addition, Yang et al [43] demonstrated that hypertrophic chondrocytes could trans-differentiate to osteoblasts and osteocytes by expressing Col1a1 and Osx during osteochondral bone formation. Although Ncam importantly regulates mesenchymal condensation during chondrogenesis [9], it also highly expresses in preosteoblastic cells during endochondral ossification [28,44]. Therefore, significant upregulation of Col1a1, Osx and Ncam by the chondrogenic induction at the late stage would be partly explained by occurrence of endochondral ossification in a mature chondrogenic cell population in OCI-iPSC constructs.…”

“…Mesenchymal condensation, i.e., densely packed aggregation of mesenchymal cells, occurs during the development of almost all tissues, including cartilage and bone [9]. Mesenchymal condensation is initiated by a signaling pathway involving cell adhesion molecules, such as Ncam.…”

“…In addition, iPSCs have an intrinsic ability to form cell aggregates, so-called embryoid bodies (EB), by floating culture in growth medium. Efficient production of EBs using culture devices such as micro-space culture plates [8] would be advantageous to induce cell condensation, which is an essential step in the self-organizing process for skeletal formation [9].…”

Developmental plasticity associated with early structural integration and evolutionary patterns: Examples of developmental bias and developmental facilitation in the skeletal system

“…placodes, anlagen) form-may have implications for expression of developmental plasticity and consequently variants available for selection (Pavlicev et al, 2011). In the skeletal system, the condensation stage is when many organs or structures establish proportions and interactions, so selection at this stage affects size, shape, number and integration of organs (Giffin et al, 2019;Atchley and Hall, 1991). In the skeletal system, the condensation stage is when many organs or structures establish proportions and interactions, so selection at this stage affects size, shape, number and integration of organs (Giffin et al, 2019;Atchley and Hall, 1991).…”

“…The early development of bones is studied as a 4-step process: migration of cells (e.g., neural crest cells or somite derivatives), epithelial-mesenchymal interactions, condensation formation, and differentiation (Giffin, Gaitor, & Franz-Odendaal, 2019;Hall & Miyake, 1995). The early development of bones is studied as a 4-step process: migration of cells (e.g., neural crest cells or somite derivatives), epithelial-mesenchymal interactions, condensation formation, and differentiation (Giffin, Gaitor, & Franz-Odendaal, 2019;Hall & Miyake, 1995).…”