The cuticle forms an apical extracellular-matrix (ECM) that covers exposed organs, such as epidermis, trachea and gut, for organizing morphogenesis and protection of insects. Recently, we reported that cuticle proteins and chitin are involved in ECM formation. However, molecular mechanisms that control assembly, maturation and replacement of the ECM and its components are not well known. Here we investigated the poorly described glyco-18-domain hydrolase family in Drosophila and identified the Chitinases (Chts) and imaginal-disc-growth-factors (Idgfs) that are essential for larval and adult molting. We demonstrate that Cht and idgf depletion results in deformed cuticles, larval and adult molting defects, and insufficient protection against wounding and bacterial infection, which altogether leads to early lethality. We show that Cht2/Cht5/Cht7/Cht9/Cht12 and idgf1/idgf3/idgf4/idgf5/idgf6 are needed for organizing proteins and chitin-matrix at the apical cell surface. Our data indicate that normal ECM formation requires Chts, which potentially hydrolyze chitin-polymers. We further suggest that the nonenzymatic idgfs act as structural proteins to maintain the ECM scaffold against chitinolytic degradation. Conservation of Chts and Idgfs proposes analogous roles in ECM dynamics across the insect taxa, indicating that Chts/Idgfs are new targets for species specific pest control.The epithelial apical extracellular matrix (ECM) controls development and structural maintenance of organisms, organ morphogenesis, wound healing, cell signaling, and the local defense barrier against a hostile environment 1,2 . Numerous events, such as tissue metamorphosis and remodeling, require dynamic alterations and degradations of the ECM architecture. Epithelial cells secrete essential components, such as proteins, lipids and polysaccharides, into the extracellular space where they form a complex network of proteins and proteoglycans. These extracellular components, together with apical membrane bound proteins, organize the ECM as a first barrier at the epithelial cell surface 2-5 .In mice and humans mutations of the extracellular collagen and the cornified envelope have been linked to skin disorder diseases, characterized by skin fragility, painful wounding and accompanied skin infections. The skin layers establish stability and an essential protective barrier by crosslinking of extracellular components 5,6 . In chitinous invertebrates, the ECM barrier is represented by the cuticle, an exoskeleton that covers the body and internal organs as an epithelial surface layer 7,8 . The cuticle is a highly organized ECM structure composed of the polysaccharide chitin and a variety of proteins and enzymes 4 . This exoskeleton is essential for body size control, epithelial barrier formation, epidermal wound healing and protects cells from direct contact with pathogens, toxins or pesticides 1,9,10 . It further provides barriers for maintaining homeostasis of body fluids 11 .Genes involved in the biosynthesis and secretion of chitin-ECM components h...