Genetic screen in Drosophila melanogaster uncovers a novel set of genes required for embryonic epithelial repair.
The wound healing response is an essential mechanism to maintain the integrity of epithelia and protect all organisms from the surrounding milieu. In the "purse-string" mechanism of wound closure, an injured epithelial sheet cinches its hole closed via an intercellular contractile actomyosin cable. This process is conserved across species and utilized by both embryonic as well as adult tissues, but remains poorly understood at the cellular level. In an effort to identify new players involved in purse-string wound closure we developed a wounding strategy suitable for screening large numbers of Drosophila embryos. Using this methodology, we observe wound healing defects in Jun-related antigen (encoding DJUN) and scab (encoding Drosophila alphaPS3 integrin) mutants and performed a forward genetics screen on the basis of insertional mutagenesis by transposons that led to the identification of 30 lethal insertional mutants with defects in embryonic epithelia repair. One of the mutants identified is an insertion in the karst locus, which encodes Drosophila beta(Heavy)-spectrin. We show beta(Heavy)-spectrin (beta(H)) localization to the wound edges where it presumably exerts an essential function to bring the wound to normal closure.
Campos
Isabel
I
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal and Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Geiger
Jennifer A
JA
Santos
Ana Catarina
AC
Carlos
Vanessa
V
Jacinto
Antonio
A
D000199:Actins / Q000235:genetics; D000818:Animals; D022081:Cell Surface Extensions / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism / Q000502:physiology*; D017344:Genes, Insect / Q000235:genetics*; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D016254:Mutagenesis, Insertional; D020033:Protein Isoforms / Q000235:genetics; D015203:Reproducibility of Results; D013049:Spectrin / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
D000199:Actins; D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D020033:Protein Isoforms; C112961:kst protein, Drosophila; D013049:Spectrin; D048031:JNK Mitogen-Activated Protein Kinases