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Role and mechanisms of the embryonic dorsal midline formation in neural development. Molecular signalling, proliferation and cell survival

We have previously shown that the specification of the structures that compose the embryonic dorsal midline (DML) in Xenopus laevis is modulated by Delta-Notch signalling. By activating its target gene hairy2a, Notch triggers a binary decision within the Spemann’s organiser, favouring the floor plate fate at the expense of the notochord (López et al., 2003; 2005). Recent evidences suggest that neuralisation in Xenopus begins before the formation of the Spemann’s organiser. The aims of this research topic are to study neural induction, patterning, survival and proliferation in the absence of DML structures after molecular ablation of the organiser. We will also study the role of Numb, Sonic Hedgehog and retinoid signalling in the molecular and cellular organisation of the floor plate in Xenopus.

Role of Notch signaling in the early development of Xenopus

Preliminary results suggest that the control of Notch signalling on the DML structures may be extensive to the entire marginal zone, by promoting neural fates at the expense of mesoderm. In addition, we have recently found that Notch is able to down-regulate the expression of chordin in the BCNE center, suggesting earlier functions for this signaling pathway that may be cross-talking with the Wnt/ß-catenin cascade during dorsal determination.
We also described that overexpression of hairy-2a represses the pan mesodermal marker brachyury in all locations and the dorsal marker chordin in the Spemann-Mangold organiser. However, chordin is ectopically activated in ventral and lateral locations, where the normal expression of hairy-2a is lower or undetectable (López et al., 2005). Preliminary results suggest that brachyury and hairy-2a may be involved in a cross-regulatory network controlling dorsal and ventral fates.
The aims of this research topic are to study: A) The role of Notch in the development of the BCNE center and possible interactions with the Wnt/ß-catenin pathway. B) Functional relationships between brachyury and hairy-2a in the development of the dorsal-ventral axis. C) The role of Notch in the marginal zone.

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Sitio de la Facultad de MedicinaSitio de la UBA