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La calcineurine dans le contrôle de la croissance-différenciation

English title CALCINEURIN IN EPITHELIAL GROWTH-DIFFERENTIATION CONTROL
Applicant Dotto Gian-Paolo
Number 102212
Funding scheme Project funding (Div. I-III)
Research institution Centre Integratif de Genomique Faculté de Biologie et Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Cellular Biology, Cytology
Start/End 01.10.2003 - 30.09.2008
Approved amount 1'056'538.00
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All Disciplines (3)

Discipline
Cellular Biology, Cytology
Experimental Cancer Research
Dermatology

Keywords (10)

epithelial cells; keratinocytes; skin; stem cells; differentiation; cancer; calcineurin; Notch; Rho GTPases; ROCK1/2 and MRCK? kinases

Lay Summary (English)

Lead
Lay summary
We are interested in molecular mechanisms that control self-renewal of epithelial stem cell populations versus their irreversible commitment to differentiation, under normal conditions and during tumor development. We use primary keratinocytes and skin as main experimental model systems. Within the proliferative compartment of the epidermis, at least two kinds of keratinocyte populations are thought to exist : "putative stem cells", with an indefinite self renewal potential and capable of generating all other types of growing and differentiating keratinocytes; and "transient amplifying cells", capable of a limited number of cell divisions and already committed towards differentiation. Primary keratinocyte cultures contain similarly distinct populations with different: i) integrin expression levels and/or adhesive properties; ii) clonogenic growth potential; iii) ability to differentiate along distinct lineages of both interfollicular epidermis and hair follicles. Additionally, keratinocyte populations that have exited the cell cycle can be distinguished between reversibly and irreversibly committed to differentiation.We have previously investigated the role played by calcineurin, the only known serine/threonine phosphatase under calcium control, in keratinocyte growth/differentiation control. We are now focusing on the function of the small GTPase RhoA and its downstream effectors in this context. In particular, over the last year we have demonstrated that key effectors of the Rho pathway, the ROCK1/2 and MRCK? kinases, are under negative transcriptional control of Notch signaling in keratinocytes, and that their up-regulation plays an important role in control of keratinocyte stem cell potential and tumor development.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
121329 Cell-cell interactions in control of tissue homeostasis, tumor development and parasitic infection / Request for a Laser Capture Microdissection Apparatus 01.10.2008 R'EQUIP
121388 Spinning-disc Mikroskop für das künftige Zentrum für Immunologie in Epalinges 01.07.2008 R'EQUIP
122281 Notch signaling as a key determinant of Epithelial-Mesenchymal interactions in the skin 01.10.2008 Project funding (Div. I-III)

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