Specific NuRD components are required for fin regeneration in zebrafish.
BACKGROUND
Epimorphic regeneration of a missing appendage in fish and urodele amphibians involves the creation of a blastema, a heterogeneous pool of progenitor cells underneath the wound epidermis. Current evidence indicates that the blastema arises by dedifferentiation of stump tissues in the vicinity of the amputation. In response to tissue loss, silenced developmental programs are reactivated to form a near-perfect copy of the missing body part. However, the importance of chromatin regulation during epimorphic regeneration remains poorly understood.


RESULTS
We found that specific components of the Nucleosome Remodeling and Deacetylase complex (NuRD) are required for fin regeneration in zebrafish. Transcripts of the chromatin remodeler chd4a/Mi-2, the histone deacetylase hdac1/HDAC1/2, the retinoblastoma-binding protein rbb4/RBBP4/7, and the metastasis-associated antigen mta2/MTA were specifically co-induced in the blastema during adult and embryonic fin regeneration, and these transcripts displayed a similar spatial and temporal expression patterns. In addition, chemical inhibition of Hdac1 and morpholino-mediated knockdown of chd4a, mta2, and rbb4 impaired regenerative outgrowth, resulting in reduction in blastema cell proliferation and in differentiation defects.


CONCLUSIONS
Altogether, our data suggest that specialized NuRD components are induced in the blastema during fin regeneration and are involved in blastema cell proliferation and redifferentiation of osteoblast precursor cells. These results provide in vivo evidence for the involvement of key epigenetic factors in the cellular reprogramming processes occurring during epimorphic regeneration in zebrafish.
Catherine
C
Pfefferli
Fritz
F
Müller
Department of Biology, University of Fribourg, Ch, du Musée 10, CH-1700 Fribourg, Switzerland. anna.jazwinska@unifr.ch.
Anna
A
Jaźwińska
Chantal
C
Wicky
D058500:Animal Fins / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D016678:Genome / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism*; D060172:Morpholinos / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D001549:Benzamides; D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D060172:Morpholinos; D011743:Pyrimidines; D029961:Zebrafish Proteins; C523184:mocetinostat; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex