The human gene HIC1 (hypermethylated in cancer) maps to chromosome 17p13.3 and is deleted in the contiguous gene disorder Miller-Dieker syndrome (MDS) [Makos-Wales et al. (1995) Nature Med., 1, 570-577; Chong et al. (1996) Genome Res., 6, 735-741]. We isolated the murine homologue Hic1, encoding a zinc-finger protein with a poxvirus and zinc-finger (POZ) domain and mapped it to mouse chromosome 11 in a region exhibiting conserved synteny to human chromosome 17. Comparison of genomic and cDNA sequences predicts two exons for the murine Hic1. The second exon exhibits 88% identity to the human HIC1 on DNA level. During embryonic development, Hic1 is expressed in mesenchymes of the sclerotomes, lateral body wall, limb and cranio-facial regions embedding the outgrowing peripheral nerves during their differentiation. During fetal development, Hic1 additionally is expressed in mesenchymes apposed to precartilaginous condensations, at many interfaces to budding epithelia of inner organs, and weakly in muscles. We observed activation of Hic1 expression in the embryonic anlagen of many tissues displaying anomalies in MDS patients. Besides lissencephaly, MDS patients exhibit facial dysmorphism and frequently additional birth defects, e.g. anomalies of the heart, kidney, gastrointestinal tract and the limbs (OMIM 247200). Thus, HIC1 activity may correlate with the defective development of the nose, jaws, extremities, gastrointestinal tract and kidney in MDS patients.