Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton

Hoyle, Diego J.; Dranow, Daniel B.; Schilling, Thomas F.

doi:10.1242/dev.199826

Cited by 6 publications

(14 citation statements)

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“…The Ihh-Pthlh feedback loop appears to be conserved in mammalian cranial base synchondroses, although Pthlh is expressed throughout the RZ and PZ ( 94 , 95 ). A few studies in zebrafish have shown the conservation of GZ patterning mechanisms between teleost fish and mammals ( 45 , 96 ), and an earlier onset of Pthlha expression than previously described, namely at the onset of chondrogenesis and before the onset of ihha expression ( Figure 5B ) ( 46 ). Novel findings in zebrafish have also shown the potential of this model for expanding our understanding of GZ patterning, as they suggest that the Ihh-Pthlh feedback loop maintains but does not establish the GZ pattern, at least in some pharyngeal endochondral bones ( 46 ).…”

Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 74%

“…A few studies in zebrafish have shown the conservation of GZ patterning mechanisms between teleost fish and mammals ( 45 , 96 ), and an earlier onset of Pthlha expression than previously described, namely at the onset of chondrogenesis and before the onset of ihha expression ( Figure 5B ) ( 46 ). Novel findings in zebrafish have also shown the potential of this model for expanding our understanding of GZ patterning, as they suggest that the Ihh-Pthlh feedback loop maintains but does not establish the GZ pattern, at least in some pharyngeal endochondral bones ( 46 ). Instead, the zebrafish Pthlh ortholog, pthlha , and mechanical force from muscle contraction initiate the HZ and the location of subsequent ihha expression, thereby establishing the negative feedback-loop that maintains GZs ( Figure 5B ) ( 46 ).…”

Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 74%

“…The zebrafish PQ and CH synchondroses have been used to study developmental mechanisms that regulate GZ development ( 24 , 26 , 45 , 46 ). These studies have shown that, like mammalian GPs, these GZs contain similar zones of cartilage maturation (RZ, PZ, HZ), though with some interesting differences in the timing of proliferation and hypertrophy.…”

Section: Skeletal Anatomy In Adult Zebrafish and Humansmentioning

confidence: 99%

“…Pthlh represses Ihh at a distance, which sets the distance between the hypertrophic zone (HZ) and resting zone (RZ). (B) Model for the patterning of CH GZs in zebrafish based on ( 46 ). pthlha is expressed at the epiphyses of the differentiating CH.…”

Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 99%

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Zebrafish endochondral growth zones as they relate to human bone size, shape and disease

Pabic

Dranow²,

Hoyle³

et al. 2022

Front. Endocrinol.

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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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Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 74%

Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 74%

Section: Skeletal Anatomy In Adult Zebrafish and Humansmentioning

confidence: 99%

Section: Development and Cellular Architecture Of Endochondral Growth...mentioning

confidence: 99%

See 2 more Smart Citations

Zebrafish endochondral growth zones as they relate to human bone size, shape and disease

Pabic

Dranow²,

Hoyle³

et al. 2022

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This feedback loop is largely conserved in cranial base synchondroses, although Pthlh is expressed throughout the RZ and PZ 25,26 . In zebrafish this feedback loop is also initiated at the onset of chondrogenesis in the ceratohyal cartilages, prefiguring the location and presumably the size of the future GZ 27 . Possible molecular mechanisms mediating PZ size variation in cichlids include changes in Ihh and/or Pthlh expression levels as well as those of their activators or repressors.…”

Section: Discussionmentioning

confidence: 99%

Cellular basis of differential endochondral growth in Lake Malawi cichlids

Johnson

Heubel

Bredesen

et al. 2022

Developmental Dynamics

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Background The shape and size of skeletal elements is determined by embryonic patterning mechanisms as well as localized growth and remodeling during post‐embryonic development. Differential growth between endochondral growth plates underlies many aspects of morphological diversity in tetrapods but has not been investigated in ray‐finned fishes. We examined endochondral growth rates in the craniofacial skeletons of two cichlid species from Lake Malawi that acquire species‐specific morphological differences during postembryonic development and quantified cellular mechanisms underlying differential growth both within and between species. Results Cichlid endochondral growth rates vary greatly (50%‐60%) between different growth zones within a species, between different stages for the same growth zone, and between homologous growth zones in different species. Differences in cell proliferation and/or cell enlargement underlie much of this differential growth, albeit in different proportions. Strikingly, differences in extracellular matrix production do not correlate with growth rate differences. Conclusions Differential endochondral growth drives many aspects of craniofacial morphological diversity in cichlids. Cellular proliferation and enlargement, but not extracellular matrix deposition, underlie this differential growth and this appears conserved in Osteichthyes. Cell enlargement is observed in some but not all cichlid growth zones and the degree to which it occurs resembles slower growing mammalian growth plates.

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Common features of cartilage maturation are not conserved in an amphibian model

Nguyen

Gómez-Picos

Liu

et al. 2023

Developmental Dynamics

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BackgroundMouse, chick, and zebrafish undergo a highly conserved program of cartilage maturation during endochondral ossification (bone formation via a cartilage template). Standard histological and molecular features of cartilage maturation are chondrocyte hypertrophy, downregulation of the chondrogenic markers Sox9 and Col2a1, and upregulation of Col10a1. We tested whether cartilage maturation is conserved in an amphibian, the western clawed frog Xenopus tropicalis, using in situ hybridization for standard markers and a novel laser‐capture microdissection RNAseq data set. We also functionally tested whether thyroid hormone drives cartilage maturation in X tropicalis, as it does in other vertebrates.ResultsThe developing frog humerus mostly followed the standard progression of cartilage maturation. Chondrocytes gradually became hypertrophic as col2a1 and sox9 were eventually down‐regulated, but col10a1 was not up‐regulated. However, the expression levels of several genes associated with the early formation of cartilage, such as acan, sox5, and col9a2, remained highly expressed even as humeral chondrocytes matured. Greater deviances were observed in head cartilages, including the ceratohyal, which underwent hypertrophy within hours of becoming cartilaginous, maintained relatively high levels of col2a1 and sox9, and lacked col10a1 expression. Interestingly, treating frog larvae with thyroid hormone antagonists did not specifically reduce head cartilage hypertrophy, resulting rather in a global developmental delay.ConclusionThese data reveal that basic cartilage maturation features in the head, and to a lesser extent in the limb, are not conserved in X tropicalis. Future work revealing how frogs deviate from the standard cartilage maturation program might shed light on both evolutionary and health studies.

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Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton

Cited by 6 publications

References 91 publications

Zebrafish endochondral growth zones as they relate to human bone size, shape and disease

Zebrafish endochondral growth zones as they relate to human bone size, shape and disease

Cellular basis of differential endochondral growth in Lake Malawi cichlids

Common features of cartilage maturation are not conserved in an amphibian model

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