University of Oulu

Renata Prunskaite-Hyyryläinen, Ilya Skovorodkin, Qi Xu, Ilkka Miinalainen, Jingdong Shan, Seppo J. Vainio, Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract, Human Molecular Genetics, Volume 25, Issue 6, 15 March 2016, Pages 1059–1073,

Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract

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Author: Prunskaite-Hyyryläinen, Renata1; Skovorodkin, Ilya1; Xu, Qi1;
Organizations: 1Oulu Centre for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Laboratory of Developmental Biology, InfoTech Oulu, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland
2Biocenter Oulu, University of Oulu, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.1 MB)
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Language: English
Published: Oxford University Press, 2016
Publish Date: 2020-05-08


The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4EGFPCre-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells. Moreover, Wnt4 is required for the initiation of MD-forming cell migration. Application of anti-Wnt4 function-blocking antibodies after the initiation of MD elongation indicated that Wnt4 is necessary for the elongation as well, and consistent with this, cell culture wound-healing assays with NIH3T3 cells overexpressing Wnt4 promoted cell migration by comparison with controls. In contrast to the Wnt4 null embryos, some Wnt4monomeric cherry/monomeric cherry (Wnt4mCh/mCh) hypomorphic mice survived to adulthood and formed MD in ∼45% of cases. Nevertheless, the MD of the Wnt4mCh/mCh females had altered cell polarization and basement membrane deposition relative to the controls. Examination of the reproductive tract of the Wnt4mCh/mCh females indicated a poorly coiled oviduct, absence of the endometrial glands and an undifferentiated myometrium, and these mice were prone to develop a hydro-uterus. In conclusion, the results suggest that the Wnt4 gene encodes signals that are important for various aspects of female reproductive tract development.

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Series: Human molecular genetics
ISSN: 0964-6906
ISSN-E: 1460-2083
ISSN-L: 0964-6906
Volume: 25
Issue: 6
Pages: 1059 - 1073
DOI: 10.1093/hmg/ddv621
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by grants from the Academy of Finland (206038 and 121647), the Centre of Excellence Grant 2012 – 2017 of the Academy of Finland (251314), the Sigrid Jusélius Foundation and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement FP7-HEALTH-F5-2012-INNOVATION-1 EURenOmics (305608). Funding to pay the Open Access publication charges for this article was provided by Centre of Excellence Grant 2012 – 2017 of the Academy of Finland (284605).
Academy of Finland Grant Number: 206038
Detailed Information: 206038 (Academy of Finland Funding decision)
121647 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
284605 (Academy of Finland Funding decision)
Copyright information: © The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.