title: Sonic hedgehog through Gli2 and Gli3 is required for the proper development of placental labyrinth.
abstract: Sonic hedgehog (Shh) functions as a conserved morphogen in the development of various organs in metazoans ranging from Drosophila to humans. Here, we have investigated the potential roles and underlying mechanisms of Shh signaling in murine placentation. Immunostaining revealed the abundant expression of the main components of Shh pathway in both the trophectoderm of blastocysts and developing placentas. Disruption of Shh led to impaired vascularogenesis of yolk sac, less branching and malformation of placental labyrinth, thereby leading to a robust decrease in capacity of transplacental passages. Moreover, placenta-specific gene incorporation by lentiviral transduction of mouse blastocysts and blastocyst transplantation robustly knocked down the expression of Gli3 and Gli2 in placenta but not in embryos. Finally, Gli3 knockdown in Shh(-/-) placentas partially rescued the defects of both yolk sac and placental labyrinth, and robustly restored the capacity of transplacental passages. Gli2 knockdown in Shh(+/)(-) placentas affected neither the capacity of tranplacental passages nor the vascularogenesis of yolk sac, however, it partially phenocopied the labyrinthine defects of Shh(-/-) placentas. Taken together, these results uncover that both Shh/Gli2 and Shh/Gli3 signals are required for proper development of murine placentas and are possibly essential for pregnant maintenance.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Y B
authors.initials: YB
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Ruan
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: X K
authors.initials: XK
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: H B
authors.initials: HB
authors.lastname: Zhu
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, The Affiliated Children Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: L F
authors.initials: LF
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, The Affiliated Children Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: C C
authors.initials: CC
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: H B
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: X M
authors.initials: XM
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3