Role of Xrx1 in Xenopus eye and anterior brain development

The anteriormost part of the neural plate is fated to give rise to the reti na and anterior brain regions. In Xenopus, this territory is initially incl uded within the expression domain of the bicoid-class homeobox gene Xotx2 b ut very soon, at the beginning of neurulation, it becomes devoid of Xotx2 t ranscripts in spatiotemporal concomitance with the transcriptional activati on of the paired-like homeobox gene Xrx1, By use of gain- and loss-of-funct ion approaches, we have studied the role played by Xrx1 in the anterior neu ral plate and its interactions with other anterior homeobox genes. We find that, at early neurula stage Xrx1 is able to repress Xotx2 expression, thus first defining the retina-diencephalon territory in the anterior neural pl ate. Overexpression studies indicate that Xrx1 possesses a proliferative ac tivity that is coupled with the specification of anterior fate. Expression of a Xrx1 dominant repressor construct (Xrx1-EnR) results in a severe impai rment of eye and anterior brain development. Analysis of several brain mark ers in early Xrx1-EnR-injected embryos reveals that anterior deletions are preceded by a reduction of anterior gene expression domains in the neural p late, Accordingly, expression of anterior markers is abolished or decreased in animal caps coinjected with the neural inducer chordin and the Xrx1-EnR construct. The lack of expansion of mid-hindbrain markers, and the increas e of apoptosis in the anterior neural plate after Xrx1-EnR injection, indic ate that anterior deletions result from an early loss of anterior neural pr ate territories rather than posteriorization of the neuroectoderm. Altogeth er, these data suggest that Xrx1 plays a role in assigning anterior and pro liferative properties to the rostralmost part of the neural plate, thus bei ng required for eye and anterior brain development.