Mammalian BarH1 confers commissural neuron identity on dorsal cells in the spinal cord

Abstract

Commissural neurons in the spinal cord project their axons through the floor plate using a number of molecular interactions, such as netrins and their receptor DCC (deleted in colorectal cancer). However, the molecular cascades that control differentiation of commissural neurons are less characterized. A homeobox gene, MBH1 (mammalian BarH1) was expressed specifically in a subset of dorsal cells in the developing spinal cord. Transgenic mice that carried lacZ and MBH1-flanking genome sequences demonstrated that MBH1 was expressed by commissural neurons. To analyze the function of MBH1, we established an in vivo electroporation method for the transfer of DNA into the mouse spinal cord. Ectopic expression of MBH1 drove dorsal cells into the fate of commissural neurons with concomitant expression of TAG-1 (transiently expressed axonal surface glycoprotein 1) and DCC. Cells ectopically expressing MBH1 migrated to the deep dorsal horn, in which endogenous MBH1-positive cells accumulated. These results suggest that MBH1 functions upstream of TAG-1 and DCC and is involved in the fate determination of commissural neurons in the spinal cord.