Myoglianin coordinates hormonal and nutrient signaling to control metamorphosis and tissue growth in the fall armyworm

The transition from larval to pupal stage in holometabolous insects is a critical developmental decision regulated by hormonal and nutritional cues. The studies reported here revealed a central role for the TGF-β ligand Myoglianin (Myo) in integrating these signals in a major lepidopteran pest, the fall armyworm, Spodoptera frugiperda . We found that CRISPR/Cas9-mediated Myo knockout (KO) resulted in supernumerary larval molts and an impairment of the larval–pupal transition. Myo-KO larvae exhibited a disrupted hormone milieu, characterized by elevated juvenile hormone (JH) levels and reduced ecdysone levels. The elevated JH titer was associated with reduced degradation by JH esterase, whereas the decrease in ecdysteroid levels was attributable to suppressed synthesis, driven by downregulation of the PTTH signaling axis in the head and of ecdysteroid biosynthesis genes in the prothoracic glands. Furthermore, Myo KO led to disproportionate growth, with oversized larvae harboring undersized tissues (e.g., wing disc and testes). This was associated with reduced expression of genes in the insulin/TOR signaling pathway and nutrient transporters, indicating impaired nutrient allocation. Our results establish Myo as a master regulator that synchronizes systemic endocrine signals with tissue-specific nutrient responses to coordinate metamorphosis and balance growth.