The Impact of Drosophila Awd/NME1/2 Levels on Notch and Wg Signaling Pathways

• Published in: International journal of molecular sciences Vol. 21; no. 19; p. 7257
• Main Authors: Serafini, Giulia, Giordani, Giorgia, Grillini, Luca, Andrenacci, Davide, Gargiulo, Giuseppe, Cavaliere, Valeria
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2020; MDPI
• Subjects: Adults; Animals; Apoptosis; Cell Death; Chromosomal Instability; Chromosomes, Insect - chemistry; Chromosomes, Insect - metabolism; Cloning; DNA damage; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Gene expression; Gene Expression Regulation, Developmental; Insects; Isoenzymes - genetics; Isoenzymes - metabolism; Kinases; Larva - cytology; Larva - genetics; Larva - growth & development; Larva - metabolism; Male; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; Medical prognosis; Metastasis; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; Nucleoside-Diphosphate Kinase - antagonists & inhibitors; Nucleoside-Diphosphate Kinase - genetics; Nucleoside-Diphosphate Kinase - metabolism; Phenotype; Physiological aspects; Proteins; Receptors, Notch - genetics; Receptors, Notch - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Wings, Animal - cytology; Wings, Animal - growth & development; Wings, Animal - metabolism; Wnt Signaling Pathway - genetics; Wnt1 Protein - genetics; Wnt1 Protein - metabolism; Germany; Awd/NME; Wg signaling; RNAi; hypomorph; Notch signaling; chromosomal instability
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197257

Awd, the Drosophila homologue of NME1/2 metastasis suppressors, plays key roles in many signaling pathways. Mosaic analysis of the null awdJ2A4 allele showed that loss of awd gene function blocks Notch signaling and the expression of its target genes including the Wingless (Wg/Wnt1) morphogen. We also showed that RNA interference (RNAi)-mediated awd silencing (awdi) in larval wing disc leads to chromosomal instability (CIN) and to Jun amino-terminal kinases (JNK)-mediated cell death. Here we show that this cell death is independent of p53 activity. Based on our previous finding showing that forced survival of awdi-CIN cells leads to aneuploidy without the hyperproliferative effect, we investigated the Wg expression in awdi wing disc cells. Interestingly, the Wg protein is expressed in its correct dorso-ventral domain but shows an altered cellular distribution which impairs its signaling. Further, we show that RNAi-mediated knock down of awd in wing discs does not affect Notch signaling. Thus, our analysis of the hypomorphic phenotype arising from awd downregulation uncovers a dose-dependent effect of Awd in Notch and Wg signaling.