Several lines of evidence suggest that Wnt genes play a critical role in regulating development of the vertebrate embryo. To address the role that this family may play in the development of the chicken central nervous system (CNS), we have used a PCR based strategy to clone partial sequences for Wnt genes. At least six different Wnt genes are expressed in the developing CNS of the chick embryo. The domains of expression overlap either partially or completely, and are expressed in spatial domains that prefigure morphological subunits of the embryonic neural tube. Wnt-1 and Wnt-4 are first expressed in the open neural plate in the region of the presumptive mesencephalon. Wnt-3a expression is first observed in the rhombencephalic regions of the open neural plate. After neural tube closure, when the embryonic subdivisions of the neural tube became apparent, Wnt-1, Wnt-3a and Wnt-4 are all broadly expressed in partially overlapping domains in the mesencephalon and caudal diencephalon, as well as in the rhombencephalon and spinal cord. The mesencephalic expression patterns are subsequently modified such that Wnt-1 and Wnt-4 are expressed in a characteristic ring just rostral to the isthmus, at the mesencephalic/metencephalic junction; and Wnt-1 and Wnt-3a expression become restricted to the dorsal midline. Wnt-1, Wnt-3a, Wnt-4, Wnt-5a and Wnt-8b are expressed in one or two caudal subdivisions of the developing diencephalon, the synencephalon and posterior parencephalon, but do not extend ventral to the zona limitans interparencephalica. In contrast, Wnt-7b is expressed in the anterior parencephalon. Both Wnt-7b and Wnt-8b are expressed in telencephalic portions of the secondary prosencephalon. The timing and spatial distribution of Wnt-gene expression in the chick embryo further support the general hypothesis that Wnt genes play key roles in patterning the developing vertebrate nervous system.