Hedgehog signalling is required for perichondral osteoblast differentiation in zebrafish.
In tetrapod long bones, Hedgehog signalling is required for osteoblast differentiation in the perichondrium. In this work we analyse skeletogenesis in zebrafish larvae treated with the Hedgehog signalling inhibitor cyclopamine. We show that cyclopamine treatment leads to the loss of perichondral ossification of two bones in the head. We find that the Hedgehog co-receptors patched1 and patched2 are expressed in regions of the perichondrium that will form bone before the onset of ossification. We also show that cyclopamine treatment strongly reduces the expression of osteoblast markers in the perichondrium and that perichondral ossification is enhanced in patched1 mutant fish. This data suggests a conserved role for Hedgehog signalling in promoting perichondral osteoblast differentiation during vertebrate skeletal development. However, unlike what is seen during long bone development, we did not observe ectopic chondrocytes in the perichondrium when Hedgehog signalling is blocked. This result may point to subtle differences between the development of the skeleton in the skull and limb.
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, UK.
Katharina
K
Felber
Peter
P
Croucher
Henry H
HH
Roehl
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D024121:Collagen Type X; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C502546:Runx2b protein, zebrafish; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; C491715:ptch1 protein, zebrafish; C000541:cyclopamine