Role of foxA4a during gastrulation in Xenopus laevis

MURGAN, SABRINA; LÓPEZ, SILVIA LILIANA; PAGANELLI, ALEJANDRA R.; CARRASCO, ANDRÉS E.

Buenos Aires

Congreso; 4th International Meeting of the Latin American Society of Developmental Biology; 2008

Latin American Society for Developmental Biology

During gastrulation, the Spemann´s organiser emits signals that pattern the whole body plan of the Xenopus embryo. FoxA4a is one of the many transcription factors that are expressed in that crucial centre, but its function in early development is not well known. Later on, during neural tube closure, FoxA4a transcripts disappear from the organiser derived structures (notochord and floor plate) and are replaced by transcripts of the closely related gene FoxA2. Therefore, it was suggested that in frogs, during early development, FoxA4a carries out the role that FoxA2 plays in the mouse node, but no functional evidence was presented (Ruiz i Altaba et al, 1993; Mech Dev 44: 91-108). Knock-out mice of FoxA2 fail to elongate the primitive streak and lack a definitive node, notochord and morphological and functional floor plate, indicating that this gene is essential for their development (Ang and Rossant, 1994; Cell 78: 561-574). We sought to understand the role of FoxA4a and its functional relationship with FoxA2 during gastrulation in Xenopus embryos. We found that knock-down of FoxA4a with a specific antisense morpholino alters the posterior expression domain of Xnot, which marks the dorsal midline structures (notochord, floor plate and hypochord). Besides, the anterior Xnot expressing domain which demarcates the upcoming epiphysis disappears or is strongly reduced and posteriorely displaced. Remarkably, although we observe no significant effects in those embryos injected with the FoxA2 antisense morpholino alone, simultaneous knock-down of FoxA4a and FoxA2 causes a delay or even a disruption in the morphogenetic movements that take place during gastrulation, with blastopores failing to close.Our data suggest that there is a functional redundancy between FoxA4a and FoxA2, based on the severely affected phenotypes with the double knock-down. In the absence of either of them, the other one compensates for the function. These results support the hypothesis that FoxA4a has an early role during Xenopus development and is essential for proper gastrulation movements.