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Tgfbeta3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest.
Mech Dev 2010 Jul-Aug; 127(7-8):329-44MD

Abstract

Zebrafish tgfbeta3 is strongly expressed in a subpopulation of the migrating neural crest cells, developing pharyngeal arches and neurocranial cartilages. To study the regulatory role of tgfbeta3 in head skeletal formation, we knocked down tgfbeta3 in zebrafish and found impaired craniofacial chondrogenesis, evident by malformations in selected neurocranial and pharyngeal arch cartilages. Over-expressing tgfbeta3 in embryos resulted in smaller craniofacial cartilages without any gross malformations. These defects suggest that tgfbeta3 is required for normal chondrogenesis. To address the cellular mechanisms that lead to the observed malformations, we analyzed cranial neural crest development in morphant and tgfbeta3 over-expressing fish. We observed reduced pre-migratory and migratory cranial neural crest, the precursors of the neurocranial cartilage and pharyngeal arches, in tgfbeta3 knockdown embryos. In contrast, only the migratory neural crest was reduced in embryos over-expressing tgfbeta3. This raised the possibility that the reduced number of cranial neural crest cells is a result of increased apoptosis. Consistent with this, markedly elevated TUNEL staining in the midbrain and hindbrain, and developing pharyngeal arch region was observed in morphants, while tgfbeta3 over-expressing embryos showed marginally increased apoptosis in the developing pharyngeal arch region. We propose that both Tgfbeta3 suppression and over-expression result in reduced chondrocyte and osteocyte formation, but to different degrees and through different mechanisms. In Tgfbeta3 suppressed embryos, this is due to impaired formation and survival of a subpopulation of cranial neural crest cells through markedly increased apoptosis in regions containing the cranial neural crest cells, while in Tgfbeta3 over-expressing embryos, the milder phenotype is also due to a slightly elevated apoptosis in these regions. Therefore, proper cranial neural crest formation and survival, and ultimately craniofacial chondrogenesis and osteogenesis, are dependent on tight regulation of Tgfbeta3 protein levels in zebrafish.

Authors+Show Affiliations

Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20406684

Citation

Cheah, Felicia S H., et al. "Tgfbeta3 Regulation of Chondrogenesis and Osteogenesis in Zebrafish Is Mediated Through Formation and Survival of a Subpopulation of the Cranial Neural Crest." Mechanisms of Development, vol. 127, no. 7-8, 2010, pp. 329-44.
Cheah FS, Winkler C, Jabs EW, et al. Tgfbeta3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest. Mech Dev. 2010;127(7-8):329-44.
Cheah, F. S., Winkler, C., Jabs, E. W., & Chong, S. S. (2010). Tgfbeta3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest. Mechanisms of Development, 127(7-8), pp. 329-44. doi:10.1016/j.mod.2010.04.003.
Cheah FS, et al. Tgfbeta3 Regulation of Chondrogenesis and Osteogenesis in Zebrafish Is Mediated Through Formation and Survival of a Subpopulation of the Cranial Neural Crest. Mech Dev. 2010;127(7-8):329-44. PubMed PMID: 20406684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tgfbeta3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest. AU - Cheah,Felicia S H, AU - Winkler,Christoph, AU - Jabs,Ethylin Wang, AU - Chong,Samuel S, Y1 - 2010/04/18/ PY - 2009/06/24/received PY - 2010/04/14/revised PY - 2010/04/15/accepted PY - 2010/4/22/entrez PY - 2010/4/22/pubmed PY - 2011/1/19/medline SP - 329 EP - 44 JF - Mechanisms of development JO - Mech. Dev. VL - 127 IS - 7-8 N2 - Zebrafish tgfbeta3 is strongly expressed in a subpopulation of the migrating neural crest cells, developing pharyngeal arches and neurocranial cartilages. To study the regulatory role of tgfbeta3 in head skeletal formation, we knocked down tgfbeta3 in zebrafish and found impaired craniofacial chondrogenesis, evident by malformations in selected neurocranial and pharyngeal arch cartilages. Over-expressing tgfbeta3 in embryos resulted in smaller craniofacial cartilages without any gross malformations. These defects suggest that tgfbeta3 is required for normal chondrogenesis. To address the cellular mechanisms that lead to the observed malformations, we analyzed cranial neural crest development in morphant and tgfbeta3 over-expressing fish. We observed reduced pre-migratory and migratory cranial neural crest, the precursors of the neurocranial cartilage and pharyngeal arches, in tgfbeta3 knockdown embryos. In contrast, only the migratory neural crest was reduced in embryos over-expressing tgfbeta3. This raised the possibility that the reduced number of cranial neural crest cells is a result of increased apoptosis. Consistent with this, markedly elevated TUNEL staining in the midbrain and hindbrain, and developing pharyngeal arch region was observed in morphants, while tgfbeta3 over-expressing embryos showed marginally increased apoptosis in the developing pharyngeal arch region. We propose that both Tgfbeta3 suppression and over-expression result in reduced chondrocyte and osteocyte formation, but to different degrees and through different mechanisms. In Tgfbeta3 suppressed embryos, this is due to impaired formation and survival of a subpopulation of cranial neural crest cells through markedly increased apoptosis in regions containing the cranial neural crest cells, while in Tgfbeta3 over-expressing embryos, the milder phenotype is also due to a slightly elevated apoptosis in these regions. Therefore, proper cranial neural crest formation and survival, and ultimately craniofacial chondrogenesis and osteogenesis, are dependent on tight regulation of Tgfbeta3 protein levels in zebrafish. SN - 1872-6356 UR - https://www.unboundmedicine.com/medline/citation/20406684/Tgfbeta3_regulation_of_chondrogenesis_and_osteogenesis_in_zebrafish_is_mediated_through_formation_and_survival_of_a_subpopulation_of_the_cranial_neural_crest_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4773(10)00026-2 DB - PRIME DP - Unbound Medicine ER -