09-P001 Role of Flrt3 during vertebrate limb development

The apical ectodermal ridge (AER), a thickening of the limb epithelium at its distal tip, is pivotal for maintaining vertebrate limb outgrowth. In a recent study, Flrt3 has been involved in the activation of ERK by FGFs. Moreover, Flrt3 has been described as a transmembrane protein able to interact with FGF receptors modulating, this way, FGFR signaling, either directly or recruiting cytoplasmic cofactors that enhance the activation of this pathway. Preliminary results show that Flrt3 expression is restricted to the AER, colocalizing its expression with fgf8 and pERK activity. Moreover, our data indicate that Flrt3 expression is not regulated by FGF activity, although ectopic Wnt3a is able to induce Flrt3 expression. Loss-of-function studies have shown that the silencing of Flrt3 affects the integrity of AER and, subsequently, its proper activity during limb bud outgrowth. We are performing studies in order to uncover the downstream targets o the Flrt3/Erk activity.