title: The Maf factor Traffic jam both enables and inhibits collective cell migration in Drosophila oogenesis.
abstract: Border cell cluster (BCC) migration in the Drosophila ovary is an excellent system to study the gene regulatory network that enables collective cell migration. Here, we identify the large Maf transcription factor Traffic jam (Tj) as an important regulator of BCC migration. Tj has a multifaceted impact on the known core cascade that enables BCC motility, consisting of the Jak/Stat signaling pathway, the C/EBP factor Slow border cells (Slbo), and the downstream effector DE-cadherin (DEcad). The initiation of BCC migration coincides with a Slbo-dependent decrease in Tj expression. This reduction of Tj is required for normal BCC motility, as high Tj expression strongly impedes migration. At high concentration, Tj has a tripartite negative effect on the core pathway: a decrease in Slbo, an increase in the Jak/Stat inhibitor Socs36E, and a Slbo-independent reduction of DEcad. However, maintenance of a low expression level of Tj in the BCC during migration is equally important, as loss of tj function also results in a significant delay in migration concomitant with a reduction of Slbo and consequently of DEcad. Taken together, we conclude that the regulatory feedback loop between Tj and Slbo is necessary for achieving the correct activity levels of migration-regulating factors to ensure proper BCC motility.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON, M5S 3G5, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Gunawan
authors.forename: Mimi
authors.initials: M
authors.lastname: Arandjelovic
authors.forename: Dorothea
authors.initials: D
authors.lastname: Godt
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D015820:Cadherins; D029721:Drosophila Proteins; D051473:Maf Transcription Factors, Large; D011518:Proto-Oncogene Proteins; C501889:shg protein, Drosophila; C480048:tj protein, Drosophila; C077246:slbo protein, Drosophila
keywords: Border cell migration; DE-cadherin; Drosophila oogenesis; Jak/Stat; Large Maf transcription factor; Slow border cells (Slbo); Traffic jam (Tj)