title: Transient laminin beta 1a Induction Defines the Wound Epidermis during Zebrafish Fin Regeneration.
abstract: The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputated zebrafish fins. Positional cloning and complementation assays identified a temperature-sensitive allele of the ECM component laminin beta 1a (lamb1a) that blocks fin regeneration. lamb1a, but not its paralog lamb1b, is sharply induced in a subset of epithelial cells after fin amputation, where it is required to establish and maintain a polarized basal epithelial cell layer. These events facilitate expression of the morphogenetic factors shha and lef1, basolateral positioning of phosphorylated Igf1r, patterning of new osteoblasts, and regeneration of bone. By contrast, lamb1a function is dispensable for juvenile body growth, homeostatic adult tissue maintenance, repair of split fins, or renewal of genetically ablated osteoblasts. fgf20a mutations or transgenic Fgf receptor inhibition disrupt lamb1a expression, linking a central growth factor to epithelial maturation during regeneration. Our findings reveal transient induction of lamb1a in epithelial cells as a key, growth factor-guided step in formation of a signaling-competent regeneration epidermis.
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Chen-Hui
authors: CH
authors: Chen
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Alexander F
authors: AF
authors: Merriman
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America; Center for Human Disease Modeling, Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors: Jeremiah
authors: J
authors: Savage
authors: Center for Human Disease Modeling, Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors: Jason
authors: J
authors: Willer
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Taylor
authors: T
authors: Wahlig
authors: Center for Human Disease Modeling, Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors: Nicholas
authors: N
authors: Katsanis
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America; Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, United States of America.
authors: Viravuth P
authors: VP
authors: Yin
authors: Department of Cell Biology and Howard Hughes Medical Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Kenneth D
authors: KD
authors: Poss
mesh_terms: D000595:Amino Acid Sequence; D058500:Animal Fins / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D004817:Epidermis / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012038:Regeneration; D015398:Signal Transduction; D015533:Transcriptional Activation; D014945:Wound Healing; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D007797:Laminin; D029961:Zebrafish Proteins; C462526:lamb1a protein, zebrafish; D005346:Fibroblast Growth Factors