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Misexpression of R‐Spondin1 Impairs Tissue Regeneration
Author(s) -
Mathew Lijoy K.,
Andreasen Eric A.,
Tanguay Robert L.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a620-b
Subject(s) - zebrafish , regeneration (biology) , wnt signaling pathway , biology , microbiology and biotechnology , aryl hydrocarbon receptor , regulator , morpholino , gene , mutant , in situ hybridization , regulation of gene expression , gene expression , signal transduction , genetics , transcription factor
Zebrafish caudal fin regeneration is a well‐established model to evaluate the molecular mechanisms controlling regeneration. We employed a chemical inhibitory approach and demonstrated that aryl hydrocarbon receptor (AHR) activation by TCDD impairs adult and larval zebrafish fin regeneration. Global gene expression analysis performed with total RNA isolated from the regenerates of control or TCDD exposed animals revealed that R‐Spondin1(R‐Spo1) is one of the most highly TCDD‐induced genes. Morpholino‐repression of R‐Spo1 restored regeneration, despite the presence of TCDD, indicating that induction of R‐Spo1 is necessary for TCDD to block regeneration. Further, SOX9b, a developmentally important transcriptional regulator was identified as one of the most highly TCDD‐repressed genes. Since SOX9 is considered to be regulated by R‐Spo1, the functional role of SOX9b was analyzed. SOX9b homozygous mutants were able to regenerate their fin tissue, but displayed defective cartilaginous‐like support structures indicating that reduced abundance of SOX9b only partially explain the effects of AHR activation on regeneration. Since R‐Spo1 is an upstream modulator of Wnt signaling, we propose that the induction of R‐Spo1 disrupts the critical balance of Wnt signaling and the identification of the additional target genes will unravel their individual and collective roles in tissue regeneration.

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