Differential activities of Sonic hedgehog mediated by Gli transcription factors define distinct neuronal subtypes in the dorsal thalamus

The dorsal thalamus (DT) is a pivotal region in the vertebrate brain that relays inputs from the peripheral sensory organs to higher cognitive centers. It consists of clusters of neurons with relevant functions, called brain nuclei. However, the mechanisms underlying development of the DT, including specification of the neuronal subtypes and morphogenesis of the nuclear structures, remain largely unknown. As a first step to this end, we focused on two transcription factors Sox14 and Gbx2 that are expressed in the specific brain nuclei in the chick DT. The onset of their expression was found in distinct populations of the postmitotic cells in the prosomere 2, which was regulated by the differential activities of Sonic hedgehog (Shh) in a manner consistent with the action as a morphogen. Furthermore, both gain- and loss-of-function results strongly suggest that such distinct inductive activities are mediated selectively by different Gli factors. These results suggest that cooperation of the differential expression of Gli factors and the activity gradient of Shh signaling generates the distinct thalamic neurons at the specific locations. (C) 2003 Elsevier Ireland Ltd. All rights reserved.