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Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

R-Spondin1, a gene essential for lactation

R-Spondin1, a gene essential for lactation
In order to improve our understanding of the dairy performances of animals that are associated with the mammary gland, it is necessary to decode the molecular mechanisms that are involved. Our studies show that the R-Spondin1 gene is essential to the development of the mammary gland, through differentiation of the epithelial cells of the mammary gland by acting on progenitor cells.

Context and Stakes

The mammary gland plays a role on milk production. This complex organ is made up of different types of cells. In order to ensure different steps during development, the mammary gland has stem cells that are self-renewing and can give birth to many progenitor cells, which are responsible for epithelial and myoepithelial cells whose lineage and differentiation are under the influence of signals coming from a local microenvironment. One of the major roles of these adult stem cells is to proliferate in order to ensure the development of the organ and also to maintain its homeostasis.
The molecular mechanisms that regulate the maintenance of these cells have been little characterized. This is why the GFP-GM team is focusing on studies aimed at understanding the function of the R-spondin1 (Rspo1) protein in mammary gland biology. At first this protein was described as having the capacity to activate the Wnt/β-caténine pathway (Jin and Yoon, 2012), an important signaling pathway for mammary gland development in the embryo and the adult and for stem cell maintenance (van Amerongen et al., 2012).

Results

First, using mice invalidated for the Rspo1 gene, we showed that this protein was essential to the development of the mammary gland (Chadi et al., 2009). Then we characterized phenotypically and molecularly the alterations observed in absence of Rspo1 during gestation (Chadi et al., 2016). Firstly, the absence of the Rspo1 protein in the epithelial mammary gland cells caused a decrease in their proliferation followed by a defect in their terminal differentiation. Secondly, using successive transplantations of mammary gland tissue, we identified the role of Rspo1 in the maintenance of the mammary gland stem cell population in vivo.

Perspectives

Our research is aimed at improving our understanding of the molecular mechanisms that have an important role on lactation biology and the variations of dairy performances due to the environmental and/or genetic impact. To do this, we will compare the data obtained from a model species (mouse) with those from a farm species (dairy cow).

Valorisation

Chadi S., Polyte J., Lefevre L., Castille J., Ehanno A., Laubier J., Jaffrezic F., Le Provost F. (2016) Phenotypic and molecular alterations in the mammary tissue of R-spondin1 Knock-Out mice during pregnancy. PloS One. 11 : e0162566.

Chadi S., Buscara L., Pechoux C., Costa J., Laubier J., Chaboissier M.C., Pailhoux E., Vilotte J.L., Chanat E., Le Provost F. (2009) R-spondin1 is required for normal epithelial morphogenesis during mammary gland development. Biochem. Biophys. Res. Commun. 390:1040-3.

Le Provost F. Potential Rspo1 involvement in mammary stem cell function. Mammary gland biology Gordon conference, 12-17 june 2011, Salve Regina University, RI, USA (communication orale).

References

Jin YR and Yoon JK (2012) The R-spondin family of proteins: emerging regulators of WNT signaling. Int J Biochem Cell Biol. 44: 2278-87.

Van Amerongen R, Bowman AN, Nusse R (2012) Developmental stage and time dictate the fate of Wnt/β-catenin-responsive stem cells in the mammary gland.Cell Stem Cell. 11: 387-400.