title: Cx43-Dependent Skeletal Phenotypes Are Mediated by Interactions between the Hapln1a-ECM and Sema3d during Fin Regeneration.
abstract: Skeletal development is a tightly regulated process and requires proper communication between the cells for efficient exchange of information. Analysis of fin length mutants has revealed that the gap junction protein Connexin43 (Cx43) coordinates cell proliferation (growth) and joint formation (patterning) during zebrafish caudal fin regeneration. Previous studies have shown that the extra cellular matrix (ECM) protein Hyaluronan and Proteoglycan Link Protein1a (Hapln1a) is molecularly and functionally downstream of Cx43, and that hapln1a knockdown leads to reduction of the glycosaminoglycan hyaluronan. Here we find that the proteoglycan aggrecan is similarly reduced following Hapln1a knockdown. Notably, we demonstrate that both hyaluronan and aggrecan are required for growth and patterning. Moreover, we provide evidence that the Hapln1a-ECM stabilizes the secreted growth factor Semaphorin3d (Sema3d), which has been independently shown to mediate Cx43 dependent phenotypes during regeneration. Double knockdown of hapln1a and sema3d reveal synergistic interactions. Further, hapln1a knockdown phenotypes were rescued by Sema3d overexpression. Therefore, Hapln1a maintains the composition of specific components of the ECM, which appears to be required for the stabilization of at least one growth factor, Sema3d. We propose that the Hapln1a dependent ECM provides the required conditions for Sema3d stabilization and function. Interactions between the ECM and signaling molecules are complex and our study demonstrates the requirement for components of the Hapln1a-ECM for Sema3d signal transduction.
authors.affiliation: Department of Biological Sciences, 111 Research Drive, Iacocca B217, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Govindan
authors.affiliation: Department of Biological Sciences, 111 Research Drive, Iacocca B217, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Kyaw Min
authors.initials: KM
authors.lastname: Tun
authors.affiliation: Department of Biological Sciences, 111 Research Drive, Iacocca B217, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Iovine
mesh_terms: D058500:Animal Fins / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D018031:Connexin 43 / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006820:Hyaluronic Acid / Q000378:metabolism; D017403:In Situ Hybridization; D008954:Models, Biological; D060172:Morpholinos / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D039961:Semaphorins / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000099249:Proteoglycan Link Protein
chemical_list: D018031:Connexin 43; D016326:Extracellular Matrix Proteins; D006820:Hyaluronic Acid; D060172:Morpholinos; D009414:Nerve Growth Factors; D011509:Proteoglycans; D039961:Semaphorins; D029961:Zebrafish Proteins; C000594258:Hapln1a protein, zebrafish; D000099249:Proteoglycan Link Protein; C118295:sema3d protein, zebrafish
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