TY - JOUR
T1 - Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling
AU - Van Raay, Terence J.
AU - Coffey, Robert J.
AU - Solnica-Krezel, Lilianna
N1 - Funding Information:
We would like to thank members of the Solnica-Krezel and Coffey labs for support and valuable comments. We are grateful to Amy Bradshaw and Jared Ruddick for excellent fish care and Amy Bradshaw for help with the in vitro fertilizations. We are also grateful to Susan R. Opalenik, PhD and the Vanderbilt Skin Diseases Research Center Molecular Genetics Core Laboratory for qRT-PCR. RJC acknowledges the support of NCI P50 95103 Special Program of Research Excellence (SPORE), U01 084239 Mouse Models of Human Cancers Consortium (MMHCC) and RO1 CA46413. Work in the LSK lab was supported by NIH RO1 GM55101.
PY - 2007/9/15
Y1 - 2007/9/15
N2 - Wnt signaling controls a wide range of developmental processes and its aberrant regulation can lead to disease. To better understand the regulation of this pathway, we identified zebrafish homologues of Naked Cuticle (Nkd), Nkd1 and Nkd2, which have previously been shown to inhibit canonical Wnt/β-catenin signaling. Zebrafish nkd1 expression increases substantially after the mid-blastula transition in a pattern mirroring that of activated canonical Wnt/β-catenin signaling, being expressed in both the ventrolateral blastoderm margin and also in the axial mesendoderm. In contrast, zebrafish nkd2 is maternally and ubiquitously expressed. Overexpression of Nkd1 or Nkd2a suppressed canonical Wnt/β-catenin signaling at multiple stages of early zebrafish development and also exacerbated the cyclopia and axial mesendoderm convergence and extension (C&E) defect in the non-canonical Wnt/PCP mutant silberblick (slb/wnt11). Thus, Nkds are sufficient to antagonize both canonical and non-canonical Wnt signaling. Reducing Nkd function using antisense morpholino oligonucleotides resulted in increased expression of canonical Wnt/β-catenin target genes. Finally, reducing Nkd1 function in slb mutants suppressed the axial mesendoderm C&E defect. These data indicate that zebrafish Nkd1 and Nkd2 function to limit both canonical and non-canonical Wnt signaling.
AB - Wnt signaling controls a wide range of developmental processes and its aberrant regulation can lead to disease. To better understand the regulation of this pathway, we identified zebrafish homologues of Naked Cuticle (Nkd), Nkd1 and Nkd2, which have previously been shown to inhibit canonical Wnt/β-catenin signaling. Zebrafish nkd1 expression increases substantially after the mid-blastula transition in a pattern mirroring that of activated canonical Wnt/β-catenin signaling, being expressed in both the ventrolateral blastoderm margin and also in the axial mesendoderm. In contrast, zebrafish nkd2 is maternally and ubiquitously expressed. Overexpression of Nkd1 or Nkd2a suppressed canonical Wnt/β-catenin signaling at multiple stages of early zebrafish development and also exacerbated the cyclopia and axial mesendoderm convergence and extension (C&E) defect in the non-canonical Wnt/PCP mutant silberblick (slb/wnt11). Thus, Nkds are sufficient to antagonize both canonical and non-canonical Wnt signaling. Reducing Nkd function using antisense morpholino oligonucleotides resulted in increased expression of canonical Wnt/β-catenin target genes. Finally, reducing Nkd1 function in slb mutants suppressed the axial mesendoderm C&E defect. These data indicate that zebrafish Nkd1 and Nkd2 function to limit both canonical and non-canonical Wnt signaling.
KW - Bozozok
KW - Dishevelled
KW - Naked cuticle
KW - Planar cell polarity
KW - Silberblick
KW - Wnt11
KW - Wnt8
KW - β-Catenin
UR - http://www.scopus.com/inward/record.url?scp=34548400802&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2007.04.018
DO - 10.1016/j.ydbio.2007.04.018
M3 - Article
C2 - 17689523
AN - SCOPUS:34548400802
SN - 0012-1606
VL - 309
SP - 151
EP - 168
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -