Signals from the ventral midline and isthmus regulate the development of Brn3.0-expressing neurons in the midbrain

The vertebrate midbrain consists of dorsal and ventral domains, the tectum and tegmentum, which execute remarkably different developmental programs. T ectal development is characterized by radial migration of differentiating n eurons to form a laminar structure, while the tegmentum generates functiona lly diverse nuclei at characteristic positions along the neural axis. Here we show that neurons appearing early in the development of the tectum are c haracterized either by the expression of the POU-domain transcription facto r Brn3.0, or by members of the Pax and LIM families. Early neurons of the r ostral tegmentum co express Brn3.0 and Lim1/2, and caudal tegmental neurons express Islet1/2. Notochord tissue or Shh-transfected epithelial cells, tr ansplanted to the developing tectum, suppress the development of tectal neu rons, and induce the differentiation of multiple tegmental cell types. The distance from the midbrain-hindbrain boundary (MHB) determines the specific markers expressed by the tegmental neurons induced in the tectum, and the transplantation of MHB tissue adjacent to the rostral tegmentum also induce s caudal markers, demonstrating the role of MHB signals in determining the phenotype of these early midbrain neurons. Go-culture of isolated midbrain neuroepithelium with Shh-expressing cells demonstrates that Shh is sufficie nt to convert tectal neurons to a tegmental fate. In mice lacking Shh, Brn3 .0- and Pax7-expressing neurons typical of the tectum develop throughout th e ventral midbrain, and gene expression patterns characteristic of early te gmental development do not appear. Published by Elsevier Science Ireland Lt d.