The dual regulator Sufu integrates Hedgehog and Wnt signals in the early Xenopus embryo

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The dual regulator Sufu integrates Hedgehog and Wnt signals in the early Xenopus embryo. / Tan Grahn, Hooi Min; Kriebel, Martin; Hou, Shirui; Pera, Edgar.

I: Developmental Biology, Vol. 358, Nr. 1, 2011, s. 262-276.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - The dual regulator Sufu integrates Hedgehog and Wnt signals in the early Xenopus embryo

AU - Tan Grahn, Hooi Min

AU - Kriebel, Martin

AU - Hou, Shirui

AU - Pera, Edgar

PY - 2011

Y1 - 2011

N2 - Hedgehog (Hh) and Wnt proteins are important signals implicated in several aspects of embryonic development, including the early development of the central nervous system. We found that Xenopus Suppressor-of-fused (XSufu) affects neural induction and patterning by regulating the Hh/Gli and Wnt/beta-catenin pathways. Microinjection of XSufu mRNA induced expansion of the epidermis at the expense of neural plate tissue and caused enlargement of the eyes. An antisense morpholino oligonucleotide against XSufu had the opposite effect. Interestingly, both gain- and loss-of-function experiments resulted in a posterior shift of brain markers, suggesting a biphasic effect of XSufu on anteroposterior patterning. XSufu blocked early Wnt/beta-catenin signaling, as indicated by the suppression of XWnt8-induced secondary axis formation in mRNA-injected embryos, and activation of Wnt target genes in XSufu-MO-injected ectodermal explants. We show that XSufu binds to XG*i1 and X beta-catenin. In Xenopus embryos and mouse embryonic fibroblasts, Gli1 inhibits Wnt signaling under overexpression of beta-catenin, whereas beta-catenin stimulates Hh signaling under overexpression of Glil. Notably, endogenous Sufu is critically involved in this crosstalk The results suggest that XSufu may act as a common regulator of Hh and Wnt signaling and contribute to intertwining the two pathways. (C) 2011 Elsevier Inc. All rights reserved.

AB - Hedgehog (Hh) and Wnt proteins are important signals implicated in several aspects of embryonic development, including the early development of the central nervous system. We found that Xenopus Suppressor-of-fused (XSufu) affects neural induction and patterning by regulating the Hh/Gli and Wnt/beta-catenin pathways. Microinjection of XSufu mRNA induced expansion of the epidermis at the expense of neural plate tissue and caused enlargement of the eyes. An antisense morpholino oligonucleotide against XSufu had the opposite effect. Interestingly, both gain- and loss-of-function experiments resulted in a posterior shift of brain markers, suggesting a biphasic effect of XSufu on anteroposterior patterning. XSufu blocked early Wnt/beta-catenin signaling, as indicated by the suppression of XWnt8-induced secondary axis formation in mRNA-injected embryos, and activation of Wnt target genes in XSufu-MO-injected ectodermal explants. We show that XSufu binds to XG*i1 and X beta-catenin. In Xenopus embryos and mouse embryonic fibroblasts, Gli1 inhibits Wnt signaling under overexpression of beta-catenin, whereas beta-catenin stimulates Hh signaling under overexpression of Glil. Notably, endogenous Sufu is critically involved in this crosstalk The results suggest that XSufu may act as a common regulator of Hh and Wnt signaling and contribute to intertwining the two pathways. (C) 2011 Elsevier Inc. All rights reserved.

KW - Suppressor-of-fused

KW - Gli

KW - beta-Catenin

KW - Neural

KW - Xenopus

U2 - 10.1016/j.ydbio.2011.07.035

DO - 10.1016/j.ydbio.2011.07.035

M3 - Article

C2 - 21839734

VL - 358

SP - 262

EP - 276

JO - Developmental Biology

JF - Developmental Biology

SN - 1095-564X

IS - 1

ER -