[Specification of dorsal interneurons by Wnt signaling]

During development of the vertebrate central nervous system (CNS), highly proliferative cells in the ventricular zone of the neural tube serve themselves as progenitors of the various types of neurons, such as interneurons and motor neurons. In the dorsal half of the spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron; D1, D2 and D3, listed from dorsal to ventral. This study demonstrates that mouse embryos lacking both Wnt-1 and Wnt-3a are indeed defective in determination of dorsal interneurons. Generation of D1 and D2 classes of dorsal interneurons is impaired; this loss of the dorsal interneurons is compensated by a dorsal expansion of D3 interneuron populations. Most importantly, expression of BMP family proteins, which have been reported to be able to induce dorsal interneurons, is not significantly affected in these mutant embryos. Moreover, the induction of D1 and D2 class interneurons by Wnt-3a protein in the isolated medial region of chick neural plate is demonstrated. Together, these observations clearly indicate that Wnt signaling has a critical role in the generation of D1 and D2 dorsal interneurons.