The immunoglobulin-like protein Hibris functions as a dose-dependent regulator of myoblast fusion and is differentially controlled by Ras and Notch signaling

Hibris (Hbs) is a transmembrane immunoglobulin-like protein that shows exte nsive homology to Drosophila Sticks and stones (Sns) and human kidney prote in Nephrin. Hbs is expressed in embryonic visceral, somatic and pharyngeal mesoderm among other tissues. In the somatic mesoderm, Hbs is restricted to fusion competent myoblasts and is regulated by Notch and Ras signaling pat hways. Embryos that lack or overexpress hhs show a partial block of myoblas t fusion, followed by abnormal muscle morphogenesis. Abnormalities in visce ral mesoderm are also observed. In vivo mapping of functional domains sugge sts that the intracellular domain mediates Hbs activity. Hbs and its paralo g, Sins, co-localize at the cell membrane of fusion-competent myoblasts. Th e two proteins act antagonistically: loss of sits dominantly suppresses the hbs myoblast fusion and visceral mesoderm phenotypes, and enhances Hbs ove rexpression phenotypes. Data from a P-homed enhancer reporter into hbs and colocalization studies with Sns suggest that hbs is not continuously expres sed in all fusion-competent myoblasts during the fusion process. We propose that the temporal pattern of hbs expression within fusion-competent myobla sts may reflect previously undescribed functional differences within this m yoblast population.