title: The intersection of the extrinsic hedgehog and WNT/wingless signals with the intrinsic Hox code underpins branching pattern and tube shape diversity in the drosophila airways.
abstract: The tubular networks of the Drosophila respiratory system and our vasculature show distinct branching patterns and tube shapes in different body regions. These local variations are crucial for organ function and organismal fitness. Organotypic patterns and tube geometries in branched networks are typically controlled by variations of extrinsic signaling but the impact of intrinsic factors on branch patterns and shapes is not well explored. Here, we show that the intersection of extrinsic hedgehog(hh) and WNT/wingless (wg) signaling with the tube-intrinsic Hox code of distinct segments specifies the tube pattern and shape of the Drosophila airways. In the cephalic part of the airways, hh signaling induces expression of the transcription factor (TF) knirps (kni) in the anterior dorsal trunk (DTa1). kni represses the expression of another TF spalt major (salm), making DTa1 a narrow and long tube. In DTa branches of more posterior metameres, Bithorax Complex (BX-C) Hox genes autonomously divert hh signaling from inducing kni, thereby allowing DTa branches to develop as salm-dependent thick and short tubes. Moreover, the differential expression of BX-C genes is partly responsible for the anterior-to-posterior gradual increase of the DT tube diameter through regulating the expression level of Salm, a transcriptional target of WNT/wg signaling. Thus, our results highlight how tube intrinsic differential competence can diversify tube morphology without changing availabilities of extrinsic factors.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsuda
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Chie
authors.initials: C
authors.lastname: Hosono
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saigo
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; ECCPS, University of Giessen, Giessen, Germany.
authors.forename: Christos
authors.initials: C
authors.lastname: Samakovlis
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D012137:Respiratory System / Q000254:growth & development*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051155:Wnt1 Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D051155:Wnt1 Protein; C074089:kni protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila