THE ECK RECEPTOR TYROSINE KINASE IS IMPLICATED IN PATTERN-FORMATION DURING GASTRULATION, HINDBRAIN SEGMENTATION AND LIMB DEVELOPMENT

Members of the protein superfamily of transmembrane receptor tyrosine kinases are key components of intercellular signal transduction pathwa ys that elicit appropriate cellular responses to environmental cues du ring development of multicellular organisms. In a search for additiona l receptor tyrosine kinases expressed during mouse embryogenesis we cl oned the murine homolog of Eck, a member of the Eph subfamily, that ma ps to the distal region of mouse chromosome 4. Specific antisera defin ed Eck in murine embryonic cells as a glycoprotein of 130 kDa with an intrinsic autophosphorylation activity. Immunohistochemical staining a nd laser scanning microscopy revealed a dynamic and tightly regulated distribution of Eck receptor protein in the developing mouse embryo. D uring gastrulation, a high transient distribution of Eck was seen in m esodermal cells aggregating in the midline as notochordal plate. A sim ilar restriction of Eck receptor protein was apparent along the rostro caudal axis of the developing neural tube. In hindbrain neuroepithelia , Eck protein localised specifically to cells of rhombomere 4 and was also seen transiently in cells populating second and third branchial a rches and neurogenic facial crest VII-VIII and IX-X. Receptor distribu tion also implicated Eck in development of the proximodistal axis of t he limb, expression being restricted to distal regions of limb bud mes enchyme. At later stages, additional sites of Eck protein expression w ere seen in the cartilaginous model of the skeleton, tooth primordia, infundibular component of the pituitary and various fetal tissue epith elia. Taken together, our data suggest pleiotropic functions for the E ck receptor, initially in distinctive aspects of pattern formation and subsequently in development of several fetal tissues, and reveal poss ible allelism with known mouse developmental mutant loci.