FoxA3 and goosecoid promote anterior neural fate through inhibition of Wnt8a activity before the onset of gastrulation

Formation of the nervous system initially requires the acquisition of neural identity, which is achieved through the inhibition of epidermalizing factors. A regional patterning then takes place within the neural plate through the activity of caudalizing factors. These two processes are tightly regulated early in development by the dorsal organizer. Here, we show that, in zebrafish embryos, two transcription factors, FoxA3 and Goosecoid, coexpressed at the dorsal blastula margin, are required for the definition of anterior neural fate. Their inactivation results in deletions of anterior head structures associated with an increase of Wnt8 activity at the dorsal blastula margin. These phenotypes can be fully rescued by overexpression of Wnt inhibitors or by inactivation of wnt8a. Altogether, foxA3 and goosecoid cooperate to promote formation of anterior neural tissue by protecting, as early as blastula stage, presumptive anterior neural cells from an irreversible caudalization by the posteriorizing factor Wnt8a.