title: Reduced cell number in the hindgut epithelium disrupts hindgut left-right asymmetry in a mutant of pebble, encoding a RhoGEF, in Drosophila embryos.
abstract: Animals often show left-right (LR) asymmetry in their body structures. In some vertebrates, the mechanisms underlying LR symmetry breaking and the subsequent signals responsible for LR asymmetric development are well understood. However, in invertebrates, the molecular bases of these processes are largely unknown. Therefore, we have been studying the genetic pathway of LR asymmetric development in Drosophila. The embryonic gut is the first organ that shows directional LR asymmetry during Drosophila development. We performed a genetic screen to identify mutations affecting LR asymmetric development of the embryonic gut. From this screen, we isolated pebble (pbl), which encodes a homolog of a mammalian RhoGEF, Ect2. The laterality of the hindgut was randomized in embryos homozygous for a null mutant of pbl. Pbl is a multi-functional protein required for cytokinesis and the epithelial-to-mesenchymal transition in Drosophila. Consistent with Pbl's role in cytokinesis, we found reduced numbers of cells in the hindgut epithelium in pbl homozygous embryos. The specific expression of pbl in the hindgut epithelium, but not in other tissues, rescued the LR defects and reduced cell number in embryonic pbl homozygotes. Embryos homozygous for string (stg), a mutant that reduces cell number through a different mechanism, also showed LR defects of the hindgut. However, the reduction in cell number in the pbl mutants was not accompanied by defects in the specification of hindgut epithelial tissues or their integrity. Based on these results, we speculate that the reduction in cell number may be one reason for the LR asymmetry defect of the pbl hindgut, although we cannot exclude contributions from other functions of Pbl, including regulation of the actin cytoskeleton through its RhoGEF activity.
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kenjiroo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yuta
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muguruma
authors.forename: Naotaka
authors.initials: N
authors.lastname: Nakazawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatori
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Reo
authors.initials: R
authors.lastname: Maeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002452:Cell Count; D016764:Cell Polarity; D048749:Cytokinesis; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000196:embryology*; D017353:Gene Deletion; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D009928:Organ Specificity; D017354:Point Mutation; D022821:RNA Splice Sites; D017422:Sequence Analysis, DNA
chemical_list: D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; C121865:Pbl protein, Drosophila; D022821:RNA Splice Sites