PUBLICATION
Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton
- Authors
- Hoyle, D.J., Dranow, D.B., Schilling, T.F.
- ID
- ZDB-PUB-211221-11
- Date
- 2021
- Source
- Development (Cambridge, England) 149(2): (Journal)
- Registered Authors
- Schilling, Tom
- Keywords
- Cartilage hypertrophy, Danio rerio, Growth plate, Growth zone
- MeSH Terms
-
- Animals
- Chondrocytes/cytology
- Chondrocytes/metabolism
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Osteogenesis*
- Parathyroid Hormone-Related Protein/genetics
- Parathyroid Hormone-Related Protein/metabolism*
- Pyrophosphatases/genetics
- Pyrophosphatases/metabolism
- Signal Transduction
- Skull/embryology
- Skull/metabolism*
- Stress, Mechanical
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 34919126 Full text @ Development
Citation
Hoyle, D.J., Dranow, D.B., Schilling, T.F. (2021) Pthlha and mechanical force control early patterning of growth zones in the zebrafish craniofacial skeleton. Development (Cambridge, England). 149(2):.
Abstract
Secreted signals in patterning systems often induce repressive signals that shape their distributions in space and time. In developing growth plates (GPs) of endochondral long bones, Parathyroid hormone-like hormone (Pthlh) inhibits Indian hedgehog (Ihh) to form a negative feedback loop that controls GP progression and bone size. Whether similar systems operate in other bones and how they arise during embryogenesis remain unclear. We show that Pthlha expression in the zebrafish craniofacial skeleton precedes chondrocyte differentiation and restricts where cells undergo hypertrophy, thereby initiating a future GP. Loss of Pthlha leads to an expansion of cells expressing a novel early marker of the hypertrophic zone (HZ), entpd5a, and later HZ markers such as ihha, while local Pthlha misexpression induces ectopic entpd5a expression. Formation of this early pre-HZ correlates with onset of muscle contraction and requires mechanical force; paralysis leads to loss of entpd5a and ihha expression in the pre-HZ, mislocalized pthlha expression, and no subsequent ossification. These results suggest that local Pthlh sources combined with force determine HZ locations, establishing the negative feedback loop that later maintains GPs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping