Molecular programs controlling development and tissue homeostasis

Development and tissue maintenance are highly interrelated processes and molecular programs driving development and differentiation are also triggered when stem cells become activated to replace damaged or lost cells. In our research program we try to understand the transcriptional control underlying tissue development, define stem/progenitor cells in the adult organism and determine the signaling pathways involved in their maintenance and activation. As a model of choice we use the mouse, as its physiology largely reflects that of the human body and as it allows easy manipulation of its genome using transgenic and gene-targeting techniques.

Fig1.: E18.5 developing kidney stained with antibodies WT1 (blue), Pax2 (green) and DBA (red). BN) E18.5 kidney stained with antibodies against WT1 (red) and nephrin (green), a marker for glomerular podocytes.

The mammalian kidney: a paradigm for complex organ development

Kidney function is vital for the human body. It is not only required for the excretion of waste compounds, but also a central cardiovascular organ and as such involved in controlling blood pressure, bone density, electrolyte, mineral, and acid-base balance. Given this multitude of functions it is not surprising that kidney diseases belong to the most common causes of morbidity in developed countries and affect approximately 1 out of 10 adults.

Kidney development requires the tight control of proliferation, apoptosis, cellular movements and differentiation. This control is coordinated by hundreds of transcription factors that form complex networks of interaction. We employ a combination of biochemical (e.g. ChIP-Seq) and genetic techniques to dissect the function of transcriptional regulators in renal development and determine the transcriptional programs regulated by them. Several of our genetically modified mice also represent excellent models for human disease and we are using them to understand the molecular events occurring in these pathologies. Indeed, our research has identified a set of novel candidate genes that we are presently analysing for their involvement in human disease.


Fig3.: Cell lineage tracing experiments identify a novel stem/progenitor
cell population in adult adrenals.

Tissue homeostasis and repair

Tissue repair in most organs is guaranteed through resident stem/progenitor cells. While stem cells are essential for organ renewal, there exists clear evidence for an involvement in disease: Lack of activation or depletion of the stem cell pool can lead to progressive organ failure, whereas overactivation of stem cells and their transiently proliferating derivatives can cause overgrowth and cancer.

A second focus of our group is therefore to address some of the key questions in stem cell biology: What is the differentiation capacity of resident stem/progenitor cells? Which factors determine their identity and which signaling pathways control their maintenance and activation? What is the time course of activation during repair processes? Finally, what are the links between stem cells and cancer? To achieve these goals we use genetic analysis in mice including reporter strains to monitor the activity of signaling pathways, cell lineage tracing to allow fate mapping, and inducible knockout and knockin mice to specifically manipulate gene expression in the adult organism.

Fig 4.: Overactivation of signaling pathway predispose to adrenal cancer.


Last publications

A knock-in mouse line conditionally expressing the tumor suppressor WTX/AMER1. - 2017 - Genesis (New York, N.Y. : 2000) - 55 - Boutet A, Comai G, Charlet A, Jian Motamedi F, Dhib H, Bandiera R, and Schedl,A

Coronary Artery Formation Is Driven by Localized Expression of R-spondin3. - 2017 - Cell reports - 20 P1745-1754 - Da Silva F, Rocha AS, Motamedi FJ, Massa F, Basboga C, Morrison H, Wagner KD, and Schedl,A

Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary. - 2017 - Oncogene - 36 P208-218 - De Cian MC, Pauper E, Bandiera R, Vidal VP, Sacco S, Gregoire EP, Chassot AA, Panzolini C, Wilhelm D, Pailhoux E, Youssef SA, de Bruin A, Teerds K, Schedl A, Gillot I, and Chaboissier,MC

PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development. - 2016 - Nature communications - 7 P12751 - Drelon C, Berthon A, Sahut-Barnola I, Mathieu M, Dumontet T, Rodriguez S, Batisse-Lignier M, Tabbal H, Tauveron I, Lefrançois-Martinez AM, Pointud JC, Gomez-Sanchez CE, Vainio S, Shan J, Sacco S, Schedl A, Stratakis CA, Martinez A, and Val,P

Identifying Direct Downstream Targets: WT1 ChIP-Seq Analysis. - 2016 - Methods in molecular biology (Clifton, N.J.) - 1467 P177-88 - da Silva F, Massa F, and Schedl,A

Repression of CMIP transcription by WT1 is relevant to podocyte health. - 2016 - Kidney international - 90 P1298-1311 - Moktefi A, Zhang SY, Vachin P, Ory V, Henique C, Audard V, Rucker-Martin C, Gouadon E, Eccles M, Schedl A, Heidet L, Ollero M, Sahali D, and Pawlak,A

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. - 2016 - Genes & development - 30 P1389-94 - Vidal V, Sacco S, Rocha AS, da Silva F, Panzolini C, Dumontet T, Doan TM, Shan J, Rak-Raszewska A, Bird T, Vainio S, Martinez A, and Schedl,A

Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney. - 2015 - Cell reports - 12 P1325-38 - Kumar S, Liu J, Pang P, Krautzberger AM, Reginensi A, Akiyama H, Schedl A, Humphreys BD, and McMahon,AP

Alternatively spliced isoforms of WT1 control podocyte-specific gene expression. - 2015 - Kidney international - 88 P321-31 - Lefebvre J, Clarkson M, Massa F, Bradford ST, Charlet A, Buske F, Lacas-Gervais S, Schulz H, Gimpel C, Hata Y, Schaefer F, and Schedl,A

Steroidogenic organ development and homeostasis: A WT1-centric view. - 2015 - Molecular and cellular endocrinology - 408 P145-55 - Bandiera R, Sacco S, Vidal VP, Chaboissier MC, and Schedl,A

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Schedl Andreas
Group Leader

2009 Award of the French kidney foundation (Fondation du Rein)

2003 Avenir (INSERM, France)

2002 Philippe Leverhulme Prize (UK)

2001 EMBO Young Investigator Programme

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Members Team
   Vidal Valérie
   Lyraki Rodanthi
   Grabek Anaëlle
   Kozlov Vladimir
   Oikonomakos Ioannis
Engineers & Technicians
   Jian Motamedi Fariba
   Massa Filippo
Photos ...

    March 2013 - Andres Schedl Team
   1 CDD 30 mois Assistant ingenieur   Closed

    October 2012 - Andreas Schedl Team
   1 CDD 30 mois Assistant ingenieur   Closed



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