Transcriptional networks and neural differentiation

Group leader

Our research team explores the molecular mechanisms controlling the plasticity and the stability of cellular phenotypes during neural development and tumourigenesis.

Our thoughts, senses and movements are generated by the activity of thousands of distinct neural cell types, whose coordination relies in part on their spatial distribution within the central nervous system. This organisation is established during embryogenesis thanks to regulatory processes operating in time and space, controlling the maturation of neural stem and progenitor cells. Deciphering these processes constitutes our major research aim, notably by assessing how perturbing them affects cell cycle and fate.

We focus primarily on the regulation of spinal neurogenesis by transcription factors.
On the one hand, we are investigating the molecular mechanisms underlying the pleiotropic feature of these proteins’ activity. For this, we concentrate on two paralogous transcription factors, Pax3 and Pax7, which can, like many other transcription factors, either activate or repress the expression of their target genes. This versatile transcriptional potential underpins the fact that these two molecules not only control the specification but also the rate of differentiation of several progenitor cell types within the dorsal spinal cord.

On the other hand, we are assessing how the pace of differentiation of neural stem cells is set by the combinatorial activity of multiple transcription factors. We are looking at the nature of crosstalks between several transcription factors expressed in the dorsal neural tube and the functional properties emerging from these interactions.

Finally, we are studying how alterations in the activity of these spinal transcription factors can lead to the development of tumours in neural and non-neural tissues.

In the lab we use multidisciplinary approaches, encompassing classical developmental and molecular biology, imaging, computational analyses and large-scale techniques, as well as several models, ranging from amniote embryos to embryonic stem cell-derived neuroprogenitors.

Current Research Topics:
  • Structure of the gene regulatory network underpinning the establishment of cell diversity in the developing spinal cord
  • In vitro modelling of dorso-spinal development using embryonic stem cells (ESC)
  • Transcriptional regulation of cell cycle by Pax3 & Pax7
  • Transcriptional protein complexes linked to Pax3 & Pax7
  • Spatio-temporal regulation of the transcriptional potential of Pax proteins in the developing spinal cord
  • Mechanisms relaying the repressive activity of Pax proteins

Key words: stem cells, developmental biology, transcription factors, spinal cord, gene regulatory network, specification, differentiation.

Selection of publications

Duval, N., P. Daubas, C. Bourcier de Carbon, C. St Cloment, J.-Y. Tinevez, M. Lopes, V. Ribes, Robert, B. 2014. Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord. Development 141, 1726–36.

Moore S., V. Ribes, J. Terriente, D. Wilkinson, F. Relaix, J. Briscoe. 2013. Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube. Plos Genetics. 9:e1003811.

Balaskas N., A. Ribeiro, J. Panovska, E. Dessaud, N. Sasai, K.M. Page, J. Briscoe, V. Ribes. 2012. Gene regulatory logic for reading the sonic hedgehog signaling gradient in the Vertebrate neural tube. Cell. 148:273-284.

Cruz C., V. Ribes, E. Kutejova, J. Cayuso, V. Lawson, D. Norris, J. Stevens, M. Davey, K. Blight, F. Bangs, A. Mynett, E. Hirst, R. Chung, N. Balaskas, S.L. Brody, E. Marti, J. Briscoe. 2010. Foxj1 regulates floor plate cilia architecture and modifies the response of cells to sonic hedgehog signalling. Development. 137:4271-82.

Ribes V., N. Balaskas, N. Sasai, C. Cruz, E. Dessaud, J. Cayuso, S. Tozer, L.L. Yang, B. Novitch, E. Marti, J. Briscoe. 2010. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube. Genes Dev. 24:1186-200.

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