Molecular Biology of Development - URA 2578 du CNRS  

  HEADProf Jean-François Nicolas /
  MEMBERSProf Jean-François Nicolas / Dr Estelle Hirsinger / Christine Mariette / Dr Elena Tzouanacou / Dr Anne-Cécile Petit Morgane Dolez-Dixsaut / morgane.dixsaut@pasteur Inês Sequeira / Suzanne Capgras / Pascal Dardenne / Claude Legrand / Françoise Kamel /

  Annual Report

The project of the unit aims at defining at the cellular level the architecture (design) of a basic developmental process, the elongation. To fully understand a developmental process it is necessary to compare this process in several species, selected on the basis of their phylogenetic position, and also in different structures of a single species to reveal its ontogenetic plasticity. The study of cell dynamics and behaviour (growth mode, cell rearrangement, shape and size of the embryonic territories etc.) is fundamental as these factors impact the relationships between cells and between territories.

The elongation of the embryo (during gastrulation and tail bud stages) of three chordates, mouse, zebrafish and amphioxus and the elongation of a structure formed late, the hair follicle, is studied. We characterize the elements of the elongation process and attempt to define their arrangement in operational modules. These phylogenetic and ontogenetic comparisons of the same process reveal organisational principles that are perhaps shared with other developmental processes underlying formation of the body plan and of specific body structures. These studies in addition allow understanding the coupling of elongation with genetic patterning (the assignation of regulatory states to cells).

The simplest case of elongation that we have studied is the elongation of the renal tubules during their postnatal development (collaboration with M. Pontoglio). It is due to the combination of cell proliferation and mitosis orientation along the axis of the tubule during coherent growth of the structure. This has led us to propose that the elongation of this structure depends on cell polarity involving the PCP pathway.

We also have studied the elongation of the hair follicle (HF), another epithelial structure, composed of multiple layers. We have shown that elongation of internal layers is based on the directional anisotropic growth in the germinative layer within the matrix, and on the cell intercalation of its cell derivatives. Anisotropic growth is in turn the combinatorial outcome of stem mode of growth and cell division orientation. These features do not apply to the most external HF layer, adding another level of complexity to the overall process and the need of coordinating distinct cellular processes.

From our work on the formation of two axial tissues of the mouse embryo, the myotome and spinal cord the emerging picture is that directed anisotropic growth resulting from the successive production of axial derivatives from caudally located stem cell progenitors, plays a central role in the elongation of these tissues. This strategy is not used in the anterior neural tube. However, in both the anterior and posterior neural tube, cell rearrangement plays a role as indicated by the clonal patterns. We have also analysed the elongation of the surface ectoderm. Elongation of this tissue involves different combinations of growth modes depending on the position along the axis. As in the previous two cases the posterior zone in the embryo was found to be crucial. Within this zone, temporally and spatially controlled cell proliferation and cell rearrangement organize surface ectoderm elongation.

In sum it is apparent that elongation relies on the combination of basic cell operations and that the specificity of this process in different contexts depends on the manner these basic operations are arranged. In the context of the embryo, it is clear that multiple operations are involved in different tissues and these need to be coordinated within and between tissues.

Our project now is systematic large-scale clonal analysis and 4D imaging/cell tracking of the three representative chordate embryos and of the HF, to further reveal the series of operations involved in the elongation. These phylogenetic and ontogenetic comparisons of the operations involved will allow understanding the rules underlying the architecture(s) of the elongation process.

Keywords: mouse embryo, clonal analysis, 4D imaging, central nervous system, muscular system, hair follicle, amphioxus, zebrafish, developmental biology, LaacZ, chordates



Fuentes, M., Benito, E., Bertrand, S., Paris, M., Mignardot, A., Godoy, lL., Jimenez Delgado, S., Oliveri, D., Candiani, S., Hirsinger, E., d’Aniello, S., Pascual-Anaya, J., Maerso, I., Pestarino, M., Vernier, P., Nicolas, J.F., Schubert, M., Laudet, V., Genevière, A.M., Albalat, R., Garcia Fernandez, J., Holland, N.D. and Escriva, H. (2007). Insights Into Spawning Behavior and Development of the European Amphioxus (Branchiostoma lanceolatum). J Exp Zool, 308B :1-10. PMID 17520703.

Fischer, E., Legué, E., Doyen, A., Nato, F. Nicolas, J.F., Torres, V., Yaniv, M. and Pontoglio, M. (2007). Defective planar cell polarization in polycystic kidney disease. Nat Genetics, 38 (1): 21-23. PMID 16341222.

Mathis, L. and Nicolas, J.F. (2006). Clonal origin of the mammalian forebrain from widespread oriented mixing of early regionalized neuroepithelium precursors. Dev Biol, 293(1):53-63. PMID 16546156.

Legué, E. and Nicolas, J.F. (2005). Hair follicle renewal: organization of stem cells in the matrix and building of a structure by stereotyped lineages and behaviors. Development 132: 4143-54. PMID16107474.

Petit, A.C., Legué, E. and Nicolas, J.F. (2005). Methods in clonal analysis and applications. Reprod Nut Dev. 45 : 321-39.

Activity Reports 2009 - Institut Pasteur
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