Epithelial Morphogenesis and left-right asymmetry in Drosophila

Our laboratory is interested in several aspects of epithelial morphogenesis in Drosophila development.   1   we study Dorsal closure to understand how epithelial sheets undergo concerted cell shape changes leading to tissue sealing.   2   Border Cell Migration is used to try to understand the molecular mechanisms that control the transition of epithelial cells toward a migratory phenotype.   3   we recently developped a novel model in Drosophila to study how left-right asymmetry is established in invertebrates.

DORSAL CLOSURE : Dorsal Closure (DC) is a paradigm to study the sealing of epithelial sheets, a common process occurring both during normal development and after injury (wound-healing). Midway through embryogenesis, the embryo dorsal surface is "open", being covered by a squamous and transient sheet of cells (the amnioserosa) instead of epidermis like all other parts of the embryo. DC is an essential sealing process that allows the amnioserosa to be covered by flanking epidermis. This takes place through concerted cell elongation of lateral epidermis towards the dorsal midline and "zippering" of contralateral epidermal edges, which eventually fuse in a seamless fashion. Our laboratory has shown the essential role of the Drosophila JNK pathway in this process. Current projects include a genome-wide approach to identify JNK target genes in DC, using Affymetrix GeneChip Technology. Several new candidate JNK-target genes have been identified and are currently being studied. In parallel, we are developing quantitative modelling to allow accurate and sensitive analysis of DC phenotypes (in collaboration with Mathematicians).

BORDER CELL MIGRATION : Border cells (BC) represents an attractive model system to study migration of epithelial cells organized into "clusters" or "cohorts". A mature BC cluster is made of a mixed population of cells: 2 central polar cells (pc) which are surrounded by 6 outer BC (oBC). We are mostly interested into the early mechanisms leading to the assembly of the pre-migratory BC cluster. Genetic screening allowed us to identify Domeless, a receptor of the JAK/STAT signalling pathway, that plays an essential role for the recruitment of oBC by the pc. Recently, we found that basement membrane proteins assemble into an "apical cap" which undergoes an unusual and dynamic shuttling in polar cells, just before migration starts. Trancytosis through Drab5 is involved. Apical capping is transient and its shedding requires proper assembly of a mature cluster through JAK/STAT activity in oBC.

LEFT/RIGHT ASYMMETRY : Both in vertebrates and invertebrates, the establishment of left-right (L/R) asymmetry is essential for handedness, directional looping of internal organs (heart, gut...) and differenciation of the brain. Major signalling pathways have been identified in several vertebrate models that control L/R asymmetry (like the well conserved nodal pathway, retinoic acid,..), downstream of situs choice (the mechanism allowing the stereotyped, handed development of L/R asymmetric organs). However, molecular mechanisms determining situs choice remain elusive; one such mechanism may involve motile cilia inducing a net asymmetric flow in the node of several vertebrate embryos. L/R asymmetry in invertebrates is far less understood, and it is not clear whether vertebrates and invertebrates share similar mechanisms. To address this question, we recently started the study of L/R asymmetry in Drosophila. Genitalia rotation is used as a L/R marker: during metamorphosis, genitalia undergo a stereotyped 360° dextral rotation leading to the coiling of the spermiduct around the gut. Screening for mutations perturbing genitalia rotation led to the identification of several new genes involved in L/R asymmetry in Drosophila. One such gene, spin/Fas2 was shown to control the levels of juvenile hormone (a sesquiterpenoid related to retinoic acid), making the sesquiterpenoids compounds candidate conserved factors controlling L/R asymmetry. More recently, we have identified a unique mutation, inversus, which induces situs inversus totalis (100% individuals show a reversal of L/R asymmetry). This mutant is currently under analysis and should shed light onto the mechanisms controlling situs choice in Drosophila, as well as giving insights into the evolutionary conservation of L/R determination.

 

Last publications

Diversity and convergence in the mechanisms establishing L/R asymmetry in metazoa. - 2014 - EMBO reports - 15 P926-37 - Coutelis JB, González-Morales N, Géminard C, and Noselli,S

Starvation induces FoxO-dependent mitotic-to-endocycle switch pausing during Drosophila oogenesis. - 2014 - Development (Cambridge, England) - 141 P3013-21 - Jouandin P, Ghiglione C, and Noselli,S

The myosin ID pathway and left-right asymmetry in Drosophila. - 2014 - Genesis (New York, N.Y. : 2000) - 52 P471-80 - Géminard C, González-Morales N, Coutelis JB, and Noselli,S

In vivo characterization of dynein-driven nanovectors using Drosophila oocytes. - 2013 - PloS one - 8 Pe82908 - Parassol N, Bienvenu C, Boglio C, Fiorucci S, Cerezo D, Yu XM, Godeau G, Greiner J, Vierling P, Noselli S, Di Giorgio C, and Van De Bor,V

Drosophila left/right asymmetry establishment is controlled by the Hox gene abdominal-B. - 2013 - Developmental cell - 24 P89-97 - Coutelis JB, Géminard C, Spéder P, Suzanne M, Petzoldt AG, and Noselli,S

Drosophila apc regulates delamination of invasive epithelial clusters. - 2012 - Dev Biol - 368 P76-85 - De Graeve FM, Van de Bor V, Ghiglione C, Cerezo D, Jouandin P, Ueda R, Shashidhara LS, and Noselli,S

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment. - 2012 - Development - 139 P1874-84 - Petzoldt AG, Coutelis JB, Géminard C, Spéder P, Suzanne M, Cerezo D, and Noselli,S

Regulation and activity of JNK signaling in the wing disc peripodial membrane during adult morphogenesis in Drosophila. - 2011 - Int J Dev Biol - 55 P583-90 - Tripura C, Chandrika NP, Susmitha VN, Noselli S, and Shashidhara,LS

Mixer Cell formation during dorsal closure: a new developmental model of JNK-dependent natural cell reprogramming in Drosophila. - 2011 - Fly (Austin) - 5 - Gettings M, and Noselli,S

Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness. - 2011 - Development - 138 P1383-93 - Van de Bor V, Zimniak G, Cérí©zo D, Schaub S, and Noselli,S

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Noselli Stéphane
Group Leader

2013 Grand Prix Mottart

2008 Médaille d'Argent CNRS

2001 EMBO YIP

1999 ATIP CNRS

1998 Médaille de Bronze CNRS

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Members Team
Researchers
   Géminard Charles
   Ghiglione Christian
   Van de Bor Véronique
Postdocs
   Lapraz François
PreDocs
   Chougule Anil Mahaveer
Engineers & Technicians
   Cerezo Delphine
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JOB OFFERS

    May 2017 - S. Noselli Team
   1 POST-DOC position

    May 2017 - S. Noselli Team
   1 CDD Engineer 3 years

    March 2010 - S. Noselli Team
   1 CDD ingenieur en biologie   Closed

    October 2009 - S. Noselli Team
   1 PhD position   Closed

    October 2009 - S. Noselli Team
   1 POST-DOC position   Closed

    March 2009 - S. Noselli Team
   1 CDD 3 ans Ingenieur en biologie   Closed

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