Restriction of BMP4 activity domains in the developing neural tube of the mouse embryo

Bone morphogenetic protein (BMP) signals pattern the dorsal neural tube, defining distinct neuronal progenitor cell domains along the dorsoventral axis of the developing spinal cord. These dorsally expressed BMPs appear to have a limited range of action. The mechanisms that regulate this range of action are unclear. We created a GAL4/UAS bigenic mouse system to overexpress BMP4 or a mutant form of BMP4 (mutBMP4), which lacks a subset of amino-terminal basic amino acids that limits its range of action, in the dorsal neural tube. UAS-Bmp4 and UAS-mutBmp4 responder genes were activated in the dorsal neural tube by a Wnt1-GAL4 transgene. Analysis of the spinal cords of bigenic embryos that expressed comparable levels of transgenic transcripts revealed that mutBMP4 acted more ventrally in the neural tube than BMP4. This suggests that the amino-terminal basic amino-acid motif of mature BMP4 controls long-range activity for dorsoventral patterning of the vertebrate neural tube.