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Non-cell-autonomous induction of hox genes in xenopus: a transgenic approach

Ziel

In vertebrates, Hox gene expression is initiated in posterior mesoderm in the early embryo and then propagates along the anteroposterior axis independently of cell movement. The pattern of Hox gene expression is then vertically transferred from mesoderm to neurectoderm. This project aims to study the molecular and cellular aspects of these homeogenetic inductions. Recent morpholino loss of function experiments in the host laboratory indicate that these are regulated non cell autonomously by Hox genes. Several canonical signaling pathways are candidates for mediating non-cell autonomous Hox gene inductions (Retinoids, BMP, Wnt, FGF). As auto-activation is a frequent feature of Hox gene regulation, intercellular transfer of Hox proteins is also an appealing mechanism. Recent progress in frog transgenesis allows functional gene studies and the temporal and spatial expression of the gene of interest can be monitored in the embryo at the cellular level. Our strategy combines classical gain and loss of function approaches (RNA injection, morpholinos) with inducible gene Expressions. A local control of gene expression in space and time will be achieved by promoter specific Gal4-UAS system and laser activation of Hsp70 driven constructs. We propose to study the molecular mechanisms of homeogenetic induction of Hox genes expressions with a special effort devoted to the impact of retinoids pathways and intercellular Hox protein trafficking.

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NETHERLANDS INSTITUTE FOR DEVELOPMENTAL BIOLOGY
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