- PhD, Molecular Genetics, University of Strasbourg
- Postdoc, Developmental Biology, IGBMC_CNRS
- Postdoc, Developmental Biology, University of Oregon
From the fertilized egg to the fully differentiated organism, cells undergo proliferation, differentiation and morphogenesis. These different functions are controlled by sets of instructing signaling that have been conserved across evolution and that turn ON, OFF or that regulate the developmental programs required to form the different tissues and organs of a mature individual. During early embryonic development, a handful of signaling pathways, activated by a small number of secreted factors acting as morphogens, are sufficient to pattern the growing embryos along anterior-posterior and dorsal-ventral axes and to induce a bilateral asymmetry defining a left and a right side. Previous work of our lab has focused on the establishment of the dorsal-ventral axis of the zebrafish embryo through the regulation of the activity of TGFbeta superfamily members, the Bone Morphogenetic Proteins (BMPs), by specific secreted antagonists and by the Fibroblast growth factors (FGFs) signaling pathway that regulates BMP signal transduction. We also established that factors belonging to another group of the TGFbeta superfamily, the Nodal related factors, are patterning the embryo along the animal-vegetal axis therefore controlling the establishment of the definitive anterior-posterior axis of the embryo. We are now investigating the transcriptional mechanims controlling the establishment of the Left-Right asymmetry of the embryo and are characterizing the role of transcription factors downstream effectors or regulators of the Hippo signaling pathway in the formation of the zebrafish Left-right organizer. In a recent study we have discovered that a complete embryonic axis, with all proper tissues and organs can be organized by instructing uncommitted pluripotent embryonic cells with two opposing gradients of BMP and of Nodal that generate the full spectrum of combination of these two signals. Because the signaling pathways controlling early embryonic development have been conserved across evolution we predicted that results obtained using zebrafish embryonic cells can be extrapolated to mammalian embryos. Therefore, we are now inducing formation of an embryonic axis from aggregates of mouse embryonic stem cells (embryoid bodies), instructed with experimentally engineered, spatially defined, morphogen gradients. Our ultimate goal is to use this approach to generate functional tissues and organs for application in Regenerative Medicine.