Roles of a <i>Drosophila</i> ADAM 10 transmembrane metalloprotease, Kuzbanian, in tissue architecture and function of the adult adipose tissue

Various molecular mechanisms in mature adipose tissue regulate whole-body physiology. In contrast, our current understanding of the development of this tissue is limited. The adult fat body (AFB) of <i>Drosophila melanogaster</i> is an emerging model for investigating the regulatory mechanisms of adipose tissue morphogenesis in vivo. AFB precursor cells undergo long-range directional and collective migration, proliferation, and homotypic adhesion, leading to the formation of monolayered AFB during metamorphosis. Here, we show that a <i>Drosophila</i> ADAM10 transmembrane metalloprotease, Kuzbanian (Kuz), is required for the AFB morphogenesis in the precursor cells at the onset of adhesion. Histological and ultrastructural analyses revealed that the <i>kuz</i> knocked-down AFB cells formed multilayered structures or clumps, indicating that Kuz is essential for forming a single-cell-thick tissue sheet. Furthermore, adults with the morphologically altered AFB were supersensitive to starvation stress. Finally, we tested the hypothesis that Notch (N), a well-characterized substrate for Kuz or ADAM10, participates in AFB development, and found that knocking down <i>N</i> reduced AFB area coverage and made the adults less adaptive to starvation, similar to <i>kuz</i> knockdown. Altogether, our study highlights the critical role of Kuz in both the architecture and function of adult adipose tissue.