MOSIMANN ZEBRAFISH

Mechanisms of earliest hematopoietic cell fate control

Coordinatore	UNIVERSITAET ZUERICH    more  Organization address address: Raemistrasse 71 city: ZURICH postcode: 8006 contact info Titolo: Prof. Nome: Stephan Cognome: Neuhauss Email: send email Telefono: +41 44 635 60 40 Fax: +41 44 635 68 97
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2018-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITAET ZUERICH  Organization address address: Raemistrasse 71 city: ZURICH postcode: 8006 contact info Titolo: Prof. Nome: Stephan Cognome: Neuhauss Email: send email Telefono: +41 44 635 60 40 Fax: +41 44 635 68 97	CH (ZURICH)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'How blood cells and ultimately hematopoietic stem cells (HSCs) arise from uncommitted cells during development is only vaguely understood. Especially the initial formation of the first blood precursors in lateral mesoderm has been difficult to dissect. Investigating these early mechanisms of blood cell fate determination with genetic model systems provides a vital starting point for therapeutic drug discovery and the targeted manipulation of iPS cells to treat hematologic diseases. The goal of the proposed research project is to elucidate the mechanisms that drive uncommitted embryonic cells into a hematopoietic cell fate by using the vertebrate zebrafish (Danio rerio). To visualize, isolate, and fate-map the earliest stages of hematopoietic cell formation, the proposed work applies transgenic zebrafish reporters under control of the newly isolated draculin gene promoter/enhancer. draculin is the earliest marker for the emergence of hematopoietic cells from lateral mesoderm during embryo development. The transgenic labeling with draculin will be harnessed for progenitor culture assays to uncover the earliest hematopoietic cell fate potential of uncommitted lateral mesoderm. These experiments will be complemented with in vivo fate mapping using Tamoxifen-controlled Cre/lox methods. The proposed study will also apply novel zebrafish microinjection approaches to test and identify transcription factor combinations that enforce blood cell fates and HSC formation. The preliminary results revealed a combination of transcription factors that ectopically induces a hematopoietic gene program in the embryo. Altogether, this work will break new ground in our understanding of the earliest blood-forming mechanisms, and provide new insight into how cells can be experimentally guided towards the therapeutically desirable HSC fate.'