Positional cloning of a temperature-sensitive mutant emmental reveals a role for sly1 during cell proliferation in zebrafish fin regeneration.
Here, we used classical genetics in zebrafish to identify temperature-sensitive mutants in caudal fin regeneration. Gross morphological, histological, and molecular analyses revealed that one of these strains, emmental (emm), failed to form a functional regeneration blastema. Inhibition of emm function by heat treatment during regenerative outgrowth rapidly blocked regeneration. This block was associated with reduced proliferation in the proximal blastema and expansion of the nonproliferative distal blastemal zone. Positional cloning revealed that the emm phenotype is caused by a mutation in the orthologue of yeast sly1, a gene product involved in protein trafficking. sly1 is upregulated in the newly formed blastema as well as during regenerative outgrowth. Thus, sly1 is essential for blastemal organization and proliferation during two stages of fin regeneration.
Nechiporuk
Alex
A
Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. anechipo@enders.tch.harvard.edu
Poss
Kenneth D
KD
Johnson
Stephen L
SL
Keating
Mark T
MT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005121:Extremities / Q000254:growth & development / Q000502:physiology; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D007797:Laminin / Q000235:genetics / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012038:Regeneration; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013696:Temperature; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D007797:Laminin; D029961:Zebrafish Proteins; C462527:lamc1 protein, zebrafish