The development of central nervous system (CNS) neuronal networks involves processes including neuroblast migration, axonal pathfinding, and synaptogenesis. To evaluate the role of the axonal guidance molecule DSCAM in CNS connectivity, we generated a lacZ reporter construct, Pr1.8-betagal, containing a 1.8 kb fragment of the human DSCAM promoter region, and analyzed its expression in four E12.5 transgenic mouse embryos. We found that Pr1.8-betagal drives lacZ expression in the choroid plexus and roof of the fourth ventricle, the floor plate of the fourth ventricle, pons and medulla oblongata, and the eye, limb buds, and dorsal root ganglion. This recapitulates a subset of DSCAM expression as demonstrated by in situ hybridization, supporting this 1.8kb fragment as a component of the endogenous DSCAM promoter. The Pr1.8-betagal expression pattern supports a role for DSCAM in CNS development, providing an endogenous promoter to investigate the contribution of DSCAM to Down syndrome neural defects. (C) 2002 Elsevier Science (USA). All rights reserved.