Marco Milán

Institut de Recerca Biomèdica (IRB Barcelona)

Wings have provided an evolutionary advantage to insects and have allowed them to diversify. In this article, the group led by Marco Milán identified in Drosophila a highly robust regulatory mechanism that ensures the specification and growth of the wing not only during normal development but also under stress conditions. The first mutation of the wingless gene was found by accident in Drosophila in the 1970s, following the observation of flies that did not possess wings, hence its name. Fifteen years after its discovery, the gene was found to be conserved in mammals, an event that gave rise to the discovery of the wnt gene family. Mutations in wnt genes may lead to various types of cancer. The wnt gene family, including its founding member, the wingless gene, regulates several embryonic development processes in both insects and mammals. However, if this is true, then why did the first mutation of the wingless gene discovered only affect the wings of Drosophila flies? Using gene editing techniques, such as CRISPR/Cas9, the group of Marco Milán has discovered an evolutionarilyconserved genomic region that regulates the expression of the Wingless protein that is exclusively dedicated to wing specification. Using functional assays, they found out that this regulatory region not only acts to promote wing formation but it also regenerates the wings when damaged. Authors identify two evolutionary conserved cis-regulatory modules within this enhancer that are utilized in a redundant manner to mediate these two activities through the use of distinct molecular mechanisms. All these results point to evolutionarily linked conservation of wing specification and regeneration to ensure robust development of the wing, perhaps the most relevant evolutionary novelty in insects.

  • Reference:
    – Gracia-Latorre E, Pérez L, Muzzopappa M & Milán M “A single WNT enhancer drives specification and regeneration of the Drosophila wing” Nature Communications, 13(1):4794 (2022)