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IDENTIFYING AND CHARACTERIZING REGULATORS OF PRIMORDIAL VASCULAR ADVENTITIA DEVELOPMENT, ORGANIZATION AND FUNCTION

Ziel

Vascular development and function are complex processes of utmost importance to the organism involving numerous steps and cell types. One of the tissues participating in these processes is the vascular adventitia, the outermost layer of the vessel, mainly composed of connective tissue. Recently, with the association of the adventitia to a growing number of diseases, its activities have become slowly uncovered and shown to participate in a number of developmental and homeostatic processes. Despite this, the processes that regulate the development, organization and function of the primordial embryonic adventitia are still unknown.
This proposal is aimed at addressing the mechanisms and key genes regulating primordial adventitia development, organization and function. It concentrates on uncovering the molecular mechanisms underlying the activities of Tbx5, the transcription factor associated with Holt Oram Syndrome. Significantly, Tbx5 deletion during limb outgrowth leads to novel phenotypes whereby vessels form but are then ruptured as a result of an abnormal primordial adventitia organization. We have uncovered two putative target genes mediating its activities – the tumor suppressor Lysyl oxidase and the oncogene beta-Catenin. We will take advantage of the developing limb as a proven model system that allows easy access and manipulations to address the different developmental and functional aspects of the proposal. Taken together, the proposed experiments will uncover and characterize novel processes required for the development and function of the adventitia. Due to the unique properties of the adventitia, this research will set a basis for testing the relationship between a tissue's organization and function. It will enhance the understanding of the pathways that participate in the development of pluripotent, connective and vascular tissues and potentially provide novel therapeutic targets for the treatment of diseases they are implicated in.

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2011-CIG
Andere Projekte für diesen Aufruf anzeigen

Koordinator

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
EU-Beitrag
€ 100 000,00
Adresse
SENATE BUILDING TECHNION CITY
32000 Haifa
Israel

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Aktivitätstyp
Higher or Secondary Education Establishments
Kontakt Verwaltung
Mark Davison (Mr.)
Links
Gesamtkosten
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