Two transcriptional cascades orchestrate cockroach leg regeneration

Abstract

SummaryThe mystery of appendage regeneration has fascinated humans for centuries, while the regulatory mechanisms remain unclear. In this study, a transcriptional landscape of regenerating leg was established in the American cockroach,Periplaneta americana, an ideal model for appendage regeneration with remarkable regeneration capacity. Through a large-scalein vivoscreening, we identified multiple signaling pathways and transcription factors (TFs) controlling leg regeneration. Specifically,zfh-2andbowl,which have not been previously implicated in appendage regeneration, contributes to blastema proliferation and morphogenesis in two novel transcriptional cascades BMP/JAK-STAT-zfh-2-bab1/B-H2/Lim1and Notch-drm/bowl-bab1. Notably,zfh-2was found working as a direct target of BMP signaling to promote cell proliferation in the blastema. These mechanisms might be conserved in the appendage regeneration of vertebrates from an evolutionary perspective. Overall, our findings reveal that two crucial transcriptional cascades orchestrate distinct cockroach leg regeneration processes, significantly advancing the comprehension of molecular mechanism in appendage regeneration.