The engrailed-2 gene, EN2, a murine homolog of the Drosophila homeobox gene engrailed (EN), is required for midbrain and cerebellum development and dorsal ventral patterning of the limbs as well as apical ectodermal ridge formation. In Drosophila, the EN gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Human EN-1 and EN-2 are homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system. Different mutations in the mouse homologs, EN-1 and EN-2, produce different developmental defects that frequently are lethal. EN-1 is highly expressed by essentially all dopaminergic neurons in the substantia nigra and ventral tegmentum. EN-1 and EN-2 regulate expression of a-synuclein, a gene that is genetically linked to Parkinsona?s disease. During early brain development mouse EN-2 is expressed in a broad band across most of the mid-hindbrain region. EN-2 is also expressed in mouse myoblasts and has been assiciated with cerebellar hypoplasia.