The Number of Larval Molts Is Controlled by Hox in Caterpillars

Animals with exoskeletons molt for further growth. In insects, the number of larval (or nymphal) molts varies inter- and intra-specifically, and it is widely accepted that the variation in the number of larval molts is an adaptive response to diverse environmental conditions. (1-5) However, themolecular mechanism that underlies the variety and plasticity in the number of larval molts is largely unknown. In the silkworm, Bombyx mori, there are strains that molt three, four, or five times, and these numbers are determined by allelic variation at a single autosomal locus, Moltinism (M).(6-9) Here, we demonstrate that the Hox gene Sex combs reduced (Scr) is responsible for the phenotypes of the M locus. Scr is selectively expressed in the larval prothoracic gland (PG), an endocrine organ that produces molting hormones.(2) Scr represses the biosynthesis of molting hormones in the PG, thereby regulating the incremental increase in body size during each larval instar. Our experiments consistently suggest that the differential expression levels of Scr among the three M alleles result in different growth ratios that ultimately lead to the different number of larval molts. Although the role of Hox genes in conferring segmental identity along the body axis and in molding segment-specific structure later in development has been well established,(10-13) the present study identifies an unexpected role of Hox gene in hormone biosynthesis. This new role means that, in addition to shaping segment-specific morphology, Hox genes also drive the evolution of life history traits by regulating animal physiology.