Obiettivo
The long-term aim of the proposed study is to resolve the genetic and cell biological mechanisms that contribute to the establishment of vertebrate brain asymmetry. In the zebrafish forebrain, an event crucial in establishing and elaborating asymmetry is the migration of the parapineal primordium. Parapineal cells are specified bilaterally at the midline. They subsequently assemble into a rosette-like structure and migrate to the left side of the brain. The molecular basis of the cellular communication among the parapineal cells during migration is still poorly understood. Preliminary data in Dr Wilson’s group show that Fgf8 induces highly focal pathway activation prior to and during migration. Fgf-reporter activation is found only in one or a few cells that are likely at the leading edge of the migrating primordium. This reporter activation occurs concurrently with suppression of activity in adjacent cells. Our hypothesis is that Fgf pathway activation non-autonomously suppresses pathway activity in neighbouring cells thereby establishing polarity within the entire primordium. In the proposed project, I will utilise multiple techniques to address specific questions with the following immediate aims: 1) to establish how localised activation of Fgf signalling correlates with parapineal migration; 2) to determine how Fgf pathway activation non-autonomously regulates pathway activity in neighbouring cells by addressing the roles of candidate interacting pathways (Notch and Wnt); 3) to determine the molecular mechanisms that govern the cross-talk between Fgf signalling and any of the identified candidates in aim 2.
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2009-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
WC1E 6BT LONDON