title: Midline-derived Shh regulates mesonephric tubule formation through the paraxial mesoderm.
abstract: During organogenesis, Sonic hedgehog (Shh) possesses dual functions: Shh emanating from midline structures regulates the positioning of bilateral structures at early stages, whereas organ-specific Shh locally regulates organ morphogenesis at later stages. The mesonephros is a transient embryonic kidney in amniote, whereas it becomes definitive adult kidney in some anamniotes. Thus, elucidating the regulation of mesonephros formation has important implications for our understanding of kidney development and evolution. In Shh knockout (KO) mutant mice, the mesonephros was displaced towards the midline and ectopic mesonephric tubules (MTs) were present in the caudal mesonephros. Mesonephros-specific ablation of Shh in Hoxb7-Cre;Shh(flox/-) and Sall1(CreERT2/+);Shh(flox/-) mice embryos indicated that Shh expressed in the mesonephros was not required for either the development of the mesonephros or the differentiation of the male reproductive tract. Moreover, stage-specific ablation of Shh in Shh(CreERT2/flox) mice showed that notochord- and/or floor plate-derived Shh were essential for the regulation of the number and position of MTs. Lineage analysis of hedgehog (Hh)-responsive cells, and analysis of gene expression in Shh KO embryos suggested that Shh regulated nephrogenic gene expression indirectly, possibly through effects on the paraxial mesoderm. These data demonstrate the essential role of midline-derived Shh in local tissue morphogenesis and differentiation.
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Wakayama, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Murashima
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Wakayama, Japan; Faculty of Biology-Oriented Science and Technology, Kinki University, Kinokawa 649-6493, Wakayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Akita
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Wakayama, Japan; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Okazawa
authors.affiliation: Faculty of Biology-Oriented Science and Technology, Kinki University, Kinokawa 649-6493, Wakayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kishigami
authors.affiliation: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Kumamoto, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.affiliation: Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Kumamoto, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nishinakamura
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Wakayama, Japan. Electronic address: transg8@wakayama-med.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D003433:Crosses, Genetic; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D007668:Kidney / Q000502:physiology; D008297:Male; D008648:Mesoderm / Q000378:metabolism*; D008650:Mesonephros / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009672:Notochord / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; C082078:mesenchyme fork head 1 protein
keywords: Floor plate; Intermediate mesoderm; Mesonephros; Notochord; Paraxial mesoderm; Shh