Wnt1 signal determines the patterning of the diencephalic dorso-ventral axis.

Abstract

The diencephalon is a complex brain area that derives from the caudal region of the prosencephalon. This structure is divided into four longitudinal neuroepithelial zones: roof, alar, basal and floor plates, which constitute its dorso-ventral (DV) columnar domains. Morphogenetic differences between alar and basal plates in the prosencephalon and mesencephalon contribute to the characteristic expansion of alar plate derivatives in the brain and the formation of the cephalic flexure. Although differential histogenesis among DV regions seems to be relevant in understanding structural and functional complexity of the brain, most of our knowledge about DV regionalization comes from the spinal cord development. Therefore, it seems of interest to study the molecular mechanisms that govern DV patterning in the diencephalon, the brain region where strong differences in size and complexity between alar and basal derivatives are evident in all vertebrates. Different morphogenetic signals, which induce specific progenitors fate to the neighboring epithelium, are involved in the spinal cord DV patterning. To study if Wnt1, one of these signaling molecules, has a role for the establishment of the diencephalic longitudinal domains, we carried out gain- and loss-of-function experiments, using mice and chick embryos. Our results demonstrated functional differences in the molecular mechanisms downstream of Wnt1 function in the diencephalon, in relation to the spinal cord. We further demonstrated that Bmp4 signal induces Wnt1 expression in the diencephalon, unraveling a new molecular regulatory code downstream of primary dorsalizing signals to control ventral regionalization in the diencephalon.