Molecular Biology of Development - CNRS URA2578  


  HEADProf. NICOLAS Jean-François / jfnicola@pasteur.fr
  MEMBERSDIXSAUT Morgane / Dr HIRSINGER Estelle / Dr LEGUE Emilie / Dr MATHIS Luc
PETIT Anne-Cécile / Dr ROSZKO Isabelle / Dr TZOUANACOU Elena


  Annual Report

The unit exploits clonal analysis to characterize cell behaviour during the development of chordates. Cell behaviour inform about developmental strategies involved in morphogenesis. This topic complements the genetic approach that documents transcriptional networks structure and their spatio-temporal dynamics. To comprehend development we need to know how these two facets integrate and how they articulate with terminal differentiation.

Methods and model systems: These last few years, we have validated two novel clonal analysis systems that we have developed to complement the classical tissue-restricted LaacZ retrospective method.

In the first novel method (the ubiquitous LacZ system), the expression of the LacZ reporter gene is not restricted to any specific tissue. Therefore, we can detect all the cells of the clones, allowing us to address questions about cell rearrangement during embryogenesis starting from gastrulation.

In the second method (the system of temporal induction of clones), we can control when the clonal labelling starts. Therefore, we can generate saturated clonal representations of any stage of development. Depending on the reporter gene used, a global topographic analysis can be carried out at a precise time of development (LacZ reporter) or can be followed in vivo in clones (EGFP reporter).

We plan to use the 3D+t imaging to follow all the cells during the development of the zebrafish and the amphioxus. 3D+t reconstructions would allow in silico clonal analysis of the cells of a single embryo. The biological problems studied these last few years concern cell behaviour a) during the gastrulation-elongation of the embryo, during which the organs are positioned in relation to the AP and the DV axes; b) during the formation of three 3-dimensional structures, which are the layers of neuron generated by the ventricular zone in the SNC, c) the epithelial sheaths produced by the stem cells of the hair follicle (HF) and d) the adaxial cells. The identified diverse behaviours of cells play a crucial role in shaping these structures.

The example of the hair follicle

The detailed study of HF renewal using our system of temporal induction of clones has revealed that there is a particular layer of cells in the matrix juxtaposed to the dermal papilla whose cells divide following a stem mode. Our analysis has also revealed that the orientation of the division is related to the proximo-distal position. The cells produced by the germinative layer undergo a radial intercalation and a precise positioning in a predetermined clonal column. We have established a relationship between the determination of the fate of the cells and the control of cell behaviour. These two fundamental developmental operations are uncoupled. Uncoupling may be a developmental strategy that simplifies the genetic organisation of morphogenesis.

nicolas.jpg



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr