Lysyl oxidase-like 3b is critical for cartilage maturation during zebrafish craniofacial development.
Vertebrate craniofacial development requires coordinated morphogenetic interactions between the extracellular matrix (ECM) and the differentiating chondrocytes essential for cartilage formation. Recent studies reveal a critical role for specific lysyl oxidases in ECM integrity required for embryonic development. We now demonstrate that loxl3b is abundantly expressed within the head mesenchyme of the zebrafish and is critically important for maturation of neural crest derived cartilage elements. Histological and ultrastructural analyses of cartilage elements in loxl3b morphant embryos reveal abnormal maturation of cartilage and altered chondrocyte morphology. Spatiotemporal analysis of craniofacial markers in loxl3b morphant embryos shows that cranial neural crest cells migrate normally into the developing pharyngeal arches but that differentiation and condensation markers are aberrantly expressed. We further show that the loxl3b morphant phenotype is not due to P53 mediated cell death but likely to be due to reduced chondrogenic progenitor cell proliferation within the pharyngeal arches. Taken together, these data demonstrate a novel role for loxl3b in the maturation of craniofacial cartilage and can provide new insight into the specific genetic factors important in the pathogenesis of craniofacial birth defects.
Institute for Environmental Studies, VU University, Amsterdam, The Netherlands.
Antonius L
AL
van Boxtel
John M
JM
Gansner
Henk W J
HW
Hakvoort
Heather
H
Snell
Juliette
J
Legler
Jonathan D
JD
Gitlin
D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002356:Cartilage / Q000196:embryology* / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D003001:Cloning, Molecular; D005109:Extracellular Matrix / Q000235:genetics / Q000648:ultrastructure; D020868:Gene Silencing; D006257:Head / Q000196:embryology*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D013234:Stem Cells / Q000166:cytology; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D029961:Zebrafish Proteins; D000594:Amino Acid Oxidoreductases; C560438:loxl3a protein, zebrafish; C560437:loxl3b protein, zebrafish
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