The roles of FGF and WNT signaling in telencephalon development
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During development, the telencephalon gives rise to the adult structures of the cerebral hemispheres, which controls our highest intellectual processes. This complex structure derives from a simple sheet of neuroepithelial cells at the anterior end of the neural plate. However, it is not well known how the survival of these anterior neuroectodermal cells is regulated.;An organizer is a small group of cells with a remarkable inductive potency which is sufficient to induce neighboring cells to change their cell fate and organize into a normal, mirror-image duplication of their structure. Recently, loss of function studies of the inductive factors secreted by the organizer suggested that one of the organizer's functions is to actively maintain cell survival.;The Anterior Neural Ridge (ANR) located at the most anterior end of the neural plate has been suggested to act as a classic organizer for the telencephalon. So far, there are two candidate signals secreted by the ANR. One of the signals is Fibroblast Growth Factor (FGF). At least 5 FGFs are expressed at the anterior-medial end of the early CNS and there are 3 FGF receptor genes, Fgfr1, Fgfr2 and Fgfr3 that are expressed in the precursor cells of the telencephalon throughout development. We demonstrate that the removal of FGF signaling by deleting the three FGF receptors (FGFR) using a Cre-loxP system causes extensive cell death, leading to a complete loss of the telencephalon. This indicates that FGF signaling is strictly required to maintain early telencephalic precursor cell survival.;Another candidate signal is WNT/beta-catenin. In amphibians and zebrafish, an increase in WNT/beta-catenin signaling causes a loss of the telencephalon due to the failure of initiation and maintenance of telencephalic formation. In order to address the role of WNT/beta-catenin signaling in inducing the telencephalon in mouse, we used conditional loss and gain of beta-catenin functions specifically in the telencephalon. Interestingly, in beta-catenin loss of function mutants, we found massive cell death, the same phenotype as the triple FGFR mutant. In addition, we found that WNT/beta-catenin directly regulates FGF signaling. Together these results strongly suggest that WNT/beta-catenin dependent FGF signaling maintains telencephalic precursor cell survival.
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