MOUSE EYA GENES ARE EXPRESSED DURING LIMB TENDON DEVELOPMENT AND ENCODE A TRANSCRIPTIONAL ACTIVATION FUNCTION

Vertebrate limb tendons are derived from connective cells of the later al plate mesoderm, Some of the developmental steps leading to the form ation of vertebrate limb tendons have been previously identified; howe ver, the molecular mechanisms responsible for tendinous patterning and maintenance during embryogenesis are largely unknown, The eyes absent (eya) gene of Drosophila encodes a novel nuclear protein of unknown m olecular function, Here we show that Eya1 and Eya2, two mouse homologu es of Drosophila eya, are expressed initially during limb development in connective tissue precursor cells, Later in limb development, Eya1 and Eya2 expression is associated with cell condensations that form di fferent sets of limb tendons, Eya1 expression is largely restricted to flexor tendons, while Eya2 is expressed in the extensor tendons and l igaments of the phalangeal elements of the limb. These data suggest th at Eya genes participate in the patterning of the distal tendons of th e limb, To investigate the molecular functions of the Eya gene product s, we have analyzed whether the highly divergent PST (proline-serine-t hreonine)-rich N-terminal regions of Eya1-3 function as transactivatio n domains, Our results demonstrate that Ega gene products can act as t ranscriptional activators, and they support a role for this molecular function in connective tissue patterning.