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Research on the genetic mechanisms underlying human skeletal development and disease have largely relied on studies in mice. However, recently the zebrafish has emerged as a popular model for skeletal research. Despite anatomical differences such as a lack of long bones in their limbs and no hematopoietic bone marrow, both the cell types in cartilage and bone as well as the genetic pathways that regulate their development are remarkably conserved between teleost fish and humans. Here we review recent studies that highlight this conservation, focusing specifically on the cartilaginous growth zones (GZs) of endochondral bones. GZs can be unidirectional such as the growth plates (GPs) of long bones in tetrapod limbs or bidirectional, such as in the synchondroses of the mammalian skull base. In addition to endochondral growth, GZs play key roles in cartilage maturation and replacement by bone. Recent studies in zebrafish suggest key roles for cartilage polarity in GZ function, surprisingly early establishment of signaling systems that regulate cartilage during embryonic development, and important roles for cartilage proliferation rather than hypertrophy in bone size. Despite anatomical differences, there are now many zebrafish models for human skeletal disorders including mutations in genes that cause defects in cartilage associated with endochondral GZs. These point to conserved developmental mechanisms, some of which operate both in cranial GZs and limb GPs, as well as others that act earlier or in parallel to known GP regulators. Experimental advantages of zebrafish for genetic screens, high resolution live imaging and drug screens, set the stage for many novel insights into causes and potential therapies for human endochondral bone diseases.
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This content will become publicly available on January 23, 2026
A review of ectochondral bone and the role of membranes in shaping endochondral bones of the skull
Abstract Bones of the skull are traditionally categorized as derived from either endochondral or intramembranous bone. In our previous work, we have observed the interaction of different tissue types in growth of the skull. We find the dichotomy of intramembranous and endochondral bone to be too restrictive, limiting our interpretation of sources of biological variation. Here, we advocate for the use of the termectochondralbone to describe bone that originates from an endochondral model but is directed in its subsequent growth by membranes and other fascial attachments. Growth of the alisphenoid and orbitosphenoid are described as two examples of ectochondral bone, influenced in their shape primarily by the surrounding soft tissues. Ectochondral bone may be an ideal mechanism for rapidly evolving new phenotypes. Instead of evolving novelties by altering morphology of the cartilage template, novel features may be formed by ectochondral ossification, a more direct and rapid mode of osteogenesis than that of the cartilage template.
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- PAR ID:
- 10600182
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- The Anatomical Record
- Volume:
- 308
- Issue:
- 7
- ISSN:
- 1932-8486
- Format(s):
- Medium: X Size: p. 1884-1892
- Size(s):
- p. 1884-1892
- Sponsoring Org:
- National Science Foundation
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