SGDAcn is a suppressor for silk gland endoreplication and development

Silkworm silk gland cells undergo multiple rounds of endoreplication, a process in which the genome is duplicated without cell division, leading to cellular polyploidization. This results in the accumulation of genomic DNA, serving as the foundation for rapid silk proteins synthesis. For the first time, we report a previously uncharacterized gene, SGDAcn, in the silkworm silk gland that clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated nuclease 9-mediated SGDAcn knockout in the posterior silk gland increased cell size and enhanced silk production. SGDAcn knockout facilitated the progression of endoreplication by upregulating the expression of various cyclin genes and promoting energy metabolism, leading to a substantial increase in fibroin gene expression and its transcription factor Dimm, as well as the stimulation of ribosome biogenesis for messenger RNA translation and enhancement of eukaryotic translation initiation factors for protein synthesis. Our findings demonstrate that SGDAcn influences endoreplication, cell growth, and nucleolus size through SGDAcn-EGFR/PI3K/AKT and SGDAcn-NF-κB signaling pathways. Overall, SGDAcn acts as a negative regulator of silk gland development, affecting cell size and protein synthesis, thus modulating silk production. These mechanisms might be conserved in cell growth and progression, making an attractive target for genetic editing to improve silk yield in silkworms and potentially in mammalian cell growth regulation.