Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development

The Engrailed-1 gene, En1, a murine homologue of the Drosophila homeobox ge ne engrailed (en), is required for midbrain and cerebellum development and dorsa/ventral patterning of the limbs. In Drosophila, en is involved in reg ulating a number of key patterning processes including segmentation of the epidermis, An important question is whether, during evolution, the biochemi cal properties of En proteins have been conserved, revealing a common under lying molecular mechanism to their diverse developmental activities. To add ress this question, we have replaced the coding sequences of En1 with Droso phila en, Mice expressing Drosophila en in place of En1 have a near complet e rescue of the lethal En1 mutant brain defect and most skeletal abnormalit ies. In contrast, expression of Drosophila en in the embryonic limbs of En1 mutants does not lead to repression of Wnt7a in the embryonic ventral ecto derm or full rescue of the embryonic dorsal/ventral patterning defects. Fur thermore, neither En2 nor en rescue the postnatal limb abnormalities that d evelop in rare En1 null mutants that survive, These studies demonstrate tha t the biochemical activity utilized in mouse to mediate brain development h as been retained by Engrailed proteins across the phyla, and indicate that during evolution vertebrate En proteins have acquired two unique functions during embryonic and postnatal limb development and that only En1 can funct ion postnatally.