Regulation of Cell-Fate Specification in the Mouse
- Jérôme COLLIGNON
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Thanks to technological advances of the past 30 years we are beginning to understand the molecular basis of lineage specification in the early mammalian conceptus. It has been shown in the mouse, the animal model of choice, that all major signalling pathways are involved. These pathways are the same that ensure the maintenance and the renewal of tissues later in life, functions that place them at the centre of many pathological situations. The study of their implication and interplay during early developmental events, when the organism is still relatively simple, is therefore particularly relevant to our understanding of their functions in later, more complex, contexts.
The aim of our team is to understand how, in the developing mouse embryo, seemingly identical cells adopt different identities in a coordinated fashion. We focus on Nodal, a signalling molecule that plays important roles during development. Nodal is a TGFβ family member signalling via the Smad2/3 pathway, also known as the Activin/Nodal signalling pathway. The Nodal gene is required for the establishment of the anterior-posterior (AP) and left-right (LR) axes. It is also required for the specification and maintenance of various cell identities, both in embryonic and extra-embryonic lineages. One day after implantation, at E5.5, Nodal mutant embryos are smaller than wildtype, with reduced extra-embryonic ectoderm (ExE) and Epiblast (Epi). This mutant epiblast, a tissue that normally gives rise to all fetal lineages, differentiates prematurely towards anterior and neural fates. The regionalisation of the visceral endoderm is also perturbed in Nodal mutants. In particular, distal visceral endoderm (DVE) cells, which are known to play a key role in the establishment of the AP axis, fail to differentiate.
Mouse embryo development between E2.5 and E5.5
A few years ago it was found that Nodal expression starts at the blastocyst stage, as much as 48h before the first signs of the Nodal phenotype detected so far. This raised questions about the regulation and the possible functions of the gene at preimplantation stages. See our Research Activities and Projects to find out how we are currently addressing some of these questions.
Nodal expression is detected in the inner cell mass, the primitive endoderm and the epiblast
Selection of Publications
Cajal M, Lawson KA, Hill B, Moreau A, Rao J, Ross A, Collignon J, Camus A. (2012). Clonal and molecular analysis of the prospective anterior neural boundary in the mouse embryo. Development 139, 423-36.
Céline Granier, Vasily Gurchenkov, Aitana Perea-Gomez, Anne Camus, Sascha Ott, Costis Papanayotou, Julian Iranzo, Anne Moreau, John Reid, Georgy Koentges, Délara Sabéran-Djoneidi and Jérôme Collignon (2011). Nodal cis-regulatory elements reveal epiblast and primitive endoderm heterogeneity in the peri-implantation mouse embryo. Dev. Biol. 349, 350-62.
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Perea-Gomez A, Meilhac SM, Piotrowska-Nitsche K, Gray D, Collignon J, Zernicka-Goetz M. (2007). Regionalization of the mouse visceral endoderm as the blastocyst transforms into the egg cylinder. BMC Dev Biol. 7:96.
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A. Camus, A. Perea-Gomez, A. Moreau and J. Collignon. (2006). Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo. Dev. Biol. 295, 743-55.
Perea-Gomez A., Camus A., Moreau A., Grieve K., Moneron G., Dubois A., Cibert C. and Collignon J. (2004). Initiation of gastrulation in the mouse embryo is preceded by an apparent shift in the orientation of the anterior-posterior axis. Curr. Biol., 14, 197-207.
Dernière modification 23/11/2012