Smads and insect hemimetabolan metamorphosis

In contrast with Drosophila melanogaster, practically nothing is known about the involvement of the TGF-β signaling pathway in the metamorphosis of hemimetabolan insects. To partially fill this gap, we have studied the role of Smad factors in the metamorphosis of the German cockroach, Blattella germanica. In D. melanogaster, Mad is the canonical R-Smad of the BMP branch of the TGF-β signaling pathway, Smox is the canonical R-Smad of the TGF-β/Activin branch and Medea participates in both branches. In insects, metamorphosis is regulated by the MEKRE93 pathway, which starts with juvenile hormone (JH), whose signal is transduced by Methoprene-tolerant (Met), which stimulates the expression of Krüppel homolog 1 (Kr-h1) that acts to repress E93, the metamorphosis trigger. In B. germanica, metamorphosis is determined at the beginning of the sixth (final) nymphal instar (N6), when JH production ceases, the expression of Kr-h1 declines, and the transcription of E93 begins to increase. The RNAi of Mad, Smox and Medea in N6 of B. germanica reveals that the BMP branch of the TGF-β signaling pathway regulates adult ecdysis and wing extension, mainly through regulating the expression of bursicon, whereas the TGF-β/Activin branch contributes to increasing E93 and decreasing Kr-h1 at the beginning of N6, crucial for triggering adult morphogenesis, as well as to regulating the imaginal molt timing.Thanks are due to the Spanish Ministry of Economy and Competitiveness (Grants CGL2012-36251 and CGL2015-64727-P, including FEDER funds, to X.B., and a predoctoral fellowship to A.F.-N.) and to the Catalan Government (2014 SGR 619). C.G.S. received a Grant from Brazil Government (Processo CNPQ, 24574812012-L) to work in the Institute of Evolutionary Biology in Barcelona.Peer reviewe