A mitogen gradient of dorsal midline Wnts organizes growth in the CNS

Cell cycle progression and exit must be precisely patterned during development to generate tissues of the correct size, shape and symmetry. Here we present evidence that dorsal-ventral growth of the developing spinal cord is regulated by a Wnt mitogen gradient. Wnt signaling through the beta-catenin/TCF pathway positively regulates cell cycle progression and negatively regulates cell cycle exit of spinal neural precursors in part through transcriptional regulation of cyclin D1 and cyclin D2. Wnts expressed at the dorsal midline of the spinal cord, Wnt1 and Wnt3a, have mitogenic activity while more broadly expressed Wnts do not. We present several lines of evidence suggesting that dorsal midline Wnts form a…