Research Groups >  (CSC Associated Investigators)Molecular Embryology

The main focus of our research is to understand how cell fate choices are taken in the context of the mammalian embryo. Specifically, we analyse how cells in the embryo differentiate from pluripotent stem cells to mature neurons.

We study the process of neural differentiation taking a number of different approaches. In the first place we study the signalling centres that are required for neural induction, focusing on the anterior visceral endoderm (AVE), an extra-embryonic signalling centre that establishes the anterior-posterior axis of the mammalian embryo. We study how the AVE is induced, the movements the cells of the AVE undergo to reach the anterior of the embryo and how the AVE imparts anterior patterning.


Figure 1. Model for neural specification in the mouse embryo. At 5.0dpc (left panel) signalling by the TGFbeta molecule Nodal induces the AVE, the cells of the AVE then move to the anterior of the embryo where they cooperate with the axial mesendoderm to specify anterior neural identity (right panel-7.5pc).


The second approach we take is to analyse the signals that induce neural identity in the early mammalian embryo. We use genetically manipulated embryos and embryonic stem (ES) cells to gain insight into the molecular and cellular cues that underlie neural differentiation.


Figure 2. Loss of BMP signalling leads to ectopic neural differentiation. Mouse embryos lacking Bmpr1a, a receptor essential for BMP signalling, show a loss of pluripotency ( down-regulation of Oct4 and Nanog) as well as precocious and ectopic neural differentiation (up-regulation of Hesx1, Six3 and Sox1).


We study the signals that drive cells from a naïve and undifferentiated state to a neural fate and analyse how these signals are interpreted within the differentiating cells. We also screen for novel factors regulating neural differentiation. Together, these approaches provide insight into how the mammalian central nervous system is established.

Figure 3. Example of neuronal differentiation of embryonic stem cells. Triple staining for neural progenitors (Nestin –red), post-mitotic neurons (Tuj1 –green) and cell nuclei (Hoechst – blue) in a monolayer of differentiated ES cells is shown.

Molecular Embryology
Group head

Tristan Rodriguez (Dr)

Telephone 38823
Email
Group members

Sarah Bowling (Ms)

Telephone 38280
Email

Aida Di Gregorio (Ms)

Telephone 33768

Barbara Pernaute (Dr)

Juan Miguel Sanchez

Margarida Sancho (Dr)

Contact details
Telephone: +44 (0) 20 8383 8823
Facsimile: +44 (0) 20 8383 8306
Selected publications
Sancho M., Di Gregorio A., George N., Pozzi S., Sánchez J.M., Pernaute B., Rodriguez T.A. (2013). Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Developmental Cell 26: 19:30. (Recommended by F1000 Biology). Abstract

Cambray, S., Arber, C., Little, G., Dougalis, A. G., de Paola, V., Ungless, M. A., Li, M., Rodríguez, T. A., (2012). Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors. Nature communications 3. Abstract

Clements, M., Pernaute, B., Vella, F., Rodriguez, T. A. (2011). Crosstalk between Nodal/Activin and MAPK p38 signaling is essential for Anterior-Posterior axis specification. Current Biology 21, 1289–1295. Abstract

Stuckey D.W., Clements M., Di Gregorio A., Senner C.E., Srinivas S. and Rodriguez T.A. (2011). Coordination of cell proliferation and anterior-posterior axis establishment in the mouse embryo. Development 138, 1521–1530. (Recommended by F1000 Biology). Abstract

Spruce, T., Pernaute, B., Di-Gregorio, A., Cobb, B. S., Merkenschlager, M., Manzanares, M., Rodriguez, T. A. (2010). An early developmental role for mirnas in the maintenance of extraembryonic stem cells in the mouse embryo. Developmental Cell 19, 207–219. (Recommended by F1000 Biology). Abstract

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