Classical cadherins are important cell adhesion molecules specifying and separating brain nuclei and developmental compartments. Cadherin-22 (Cdh22) belongs to type II subfamily of classical cadherins, and is expressed at the midbrain-hindbrain boundary during early embryogenesis. In Fgfr1 mutant mouse embryos, which have a disturbed midbrain-hindbrain border, Cdh22 is down-regulated. Here, we studied expression of Cdh22 in developing mouse brain in more detail and compared it to expression of related family members. This revealed both complementary and overlapping patterns of Cdh22, Cdh11, Cdh8, and Cdh6 expression in distinct regions of the forebrain and midbrain. We used a mutated allele of Cdh22 to study its function in brain development. Loss of Cdh22 caused reduced postnatal viability. Despite strong Cdh22 expression in the developing brain, we did not observe defects in compartmentalization or abnormalities in the midbrain and forebrain nuclei in Cdh22 mutants. This may be explained by functional redundancy between type II cadherins. Developmental Dynamics 240:1989–2001, 2011. © 2011 Wiley-Liss, Inc.