Molecular Biology of Development (URA CNRS 2578)

Jean-François Nicolas 
jfnicola@pasteur.fr

Cell behaviour in the vertebrate embryo

We are interested in the cell behaviours and in their arrangement in spatio-temporal patterns during development, as they are at the basis of the formation of transient structures in the embryo and of the evolution of the body plan in chordates. To understand this aspect of development, we use methods of clonal analysis and in vivo imaging on several chordate models (zebrafish, chick, mouse and amphioxus).

Clonal analysis in the mouse and zebrafish

Two methods of clonal analysis are currently used in our laboratory. A method based on the use of transgenic mice harbouring a special reporter gene named LaacZ and a method based on temporally induced labelling by a recombinase fused to a mutated oestrogen (CreRT2). The LaacZ method is used in a systematic clonal analysis of cell lineages in the mouse embryo to reveal still unknown or unsuspected clonal relationships. We are also characterizing the stem cells that function during skin and hair follicle renewing and we are searching which cell behaviours are involved in the generation of hair follicle and skin shapes. Finally, these methods of clonal analysis are being adapted to the zebrafish.
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Epigenetics

Our analysis of epigenetic modification of transgenes using several LacZ reporter genes with various CpG contents has lead to the hypothesis that the mechanisms by which CpG island escapes de novo methylation is sensitive to CpG density of adjacent sequences. Further studies address the question of the molecular basis of this phenomenon. We also test these ideas with GFP and LacZ reporters introduced by homologous recombination in the Rosa 26 locus.

Cell behaviour in the chick neural tube.

The goal of our work is to gain insight into the basic mechanisms that drive the polarized expansion of the neural tube and the progression of stem cells. We combine electroporation and live imaging to analyze the sequence of cellular events that link the stem cells that organize the elongation of the spinal cord and those involved in neurons and neural crest production from the neural tube
These analyses should provide a view of the interplay between genetic and cellular patterning.
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Selected recent publications

Legué, E., Sequeira, I., Nicolas, JF. (2010). Hair follicle renewal: authentic morphogenesis that depends on a complex progression of stem cell lineages. Development 137 (4): 569-577. [PubMed]

Tzouanacou, E., Wegener, A.,  Wymeersch, F.J., Wilson, V., Nicolas, JF. (2009). Redefining the progression of lineage segregations during mammalian embryogenesis by clonal analysis. Dev. Cell 17 (3): 365-376. [PubMed] [Press Release] [Highlight Nature Reviews Genetics]

Petit AC, Nicolas JF. (2009). Large-scale clonal analysis reveals unexpected complexity in surface ectoderm morphogenesis. PLoS ONE. 4(2):e4353. [PubMed]

Fischer, E., Legué, E., Doyen, A., Nato, F., Nicolas, JF., Torres, V., Yaniv, M., Pontoglio, M. (2006). Defective planar cell polarity in polycystic kidney disease. Nat Genet. 38 (1): 21-23. [PubMed]

Roszko, I., Afonso, C., Henrique, D., Mathis, L. (2006). Key role played by RhoA in the balance between planar and apico-basal cell divisions in the chick neuroepithelium. Dev Biol. 298 (1): 212-24. [PubMed]

Mathis, L., Nicolas, JF. (2006). Clonal origin of the mammalian forebrain from widespread oriented mixing of early regionalized neuroepithelium precursors. Dev Biol. 293 (1): 53-63. [PubMed]

Legué, E., Nicolas, JF. (2005). Hair follicle renewal: organization of stem cells in the matrix and the role of stereotyped lineages and behaviors. Development 132 (18): 4143-54. [PubMed]

Meilhac SM, Esner M, Kelly RG, Nicolas JF, Buckingham ME. (2004). The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev Cell. 6 (5): 685-98. [PubMed]

Chevalier-Mariette, C., Henry, I., Montfort, L., Capgras, S., Forlani, S., Muschler, J. and Nicolas, JF. (2003). CpG content affects gene silencing in mice: evidence from novel transgenes. Genome Biol. 4 (9): R53-R5311. [PubMed]