Direct control of Hoxd1 and Irx3 expression by Wnt/beta-catenin signaling during anteroposterior patterning of the neural axis in Xenopus.

During and after gastrulation, the neural axis in vertebrates is patterned along the antero-posterior axis by the combined activity of signaling factors secreted in the neural ectoderm and the underlying mesoderm. These signals divide the neural axis into four major divisions: the forebrain, midbrain, hindbrain and spinal chord. Among the signals that pattern the neural axis, Wnts play a prominent role and many patterning genes have been found to be direct Wnt/beta-catenin target genes, including several homeobox domain-containing transcription factors. Here we show that HoxD1 and Irx3 are transcriptionally induced by the Wnt pathway during neurulation. Using induction in the presence of the translation blocking drug cycloheximide and chromatin immunoprecipitation assays, we confirm that HoxD1 and Irx3 are both direct Wnt target genes. In addition, we identified Crabp2 (cellular retinoic acid binding protein 2) as an indirect target that potentially links the activities of Wnt and retinoic acid during antero-posterior patterning.