title: Retinoic acid signaling spatially restricts osteoblasts and controls ray-interray organization during zebrafish fin regeneration.
abstract: The zebrafish caudal fin consists of repeated units of bony rays separated by soft interray tissue, an organization that must be faithfully re-established during fin regeneration. How and why regenerating rays respect ray-interray boundaries, thus extending only the existing bone, has remained unresolved. Here, we demonstrate that a retinoic acid (RA)-degrading niche is established by Cyp26a1 in the proximal basal epidermal layer that orchestrates ray-interray organization by spatially restricting osteoblasts. Disruption of this niche causes preosteoblasts to ignore ray-interray boundaries and to invade neighboring interrays where they form ectopic bone. Concomitantly, non-osteoblastic blastema cells and regenerating blood vessels spread into the interrays, resulting in overall disruption of ray-interray organization and irreversible inhibition of fin regeneration. The cyp26a1-expressing niche plays another important role during subsequent regenerative outgrowth, where it facilitates the Shha-promoted proliferation of osteoblasts. Finally, we show that the previously observed distal shift of ray bifurcations in regenerating fins upon RA treatment or amputation close to the bifurcation can be explained by inappropriate preosteoblast alignment and does not necessarily require putative changes in proximodistal information. Our findings uncover a mechanism regulating preosteoblast alignment and maintenance of ray-interray boundaries during fin regeneration.
authors.affiliation: Developmental Biology, University of Bayreuth, Bayreuth 95440, Germany RTG1331, Department of Biology, University of Konstanz, Konstanz 78457, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Blum
authors.affiliation: Developmental Biology, University of Bayreuth, Bayreuth 95440, Germany .begemann@uni-bayreuth.de.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Begemann
mesh_terms: D058500:Animal Fins / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000378:metabolism; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D000072516:Retinoic Acid 4-Hydroxylase; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C502199:cyp26b1 protein, zebrafish
keywords: Caudal fin; Cyp26a1; Interray; Osteoblast; Regeneration; Zebrafish