title: Runx/Cbfb signaling regulates postnatal development of granular convoluted tubule in the mouse submandibular gland.
abstract: BACKGROUND
  The rodent salivary gland is not fully developed at birth and the cellular definitive differentiation takes place postnatally. However, little is known about its molecular mechanism.
  
  
  RESULTS
  Here we provide the loss-of-function genetic evidence that Runx signaling affects postnatal development of the submandibular gland (SMG). Core binding factor β (Cbfb) is a cotranscription factor which forms a heterodimer with Runx proteins. Cbfb was specifically expressed in the duct epithelium, specifically in the SMG. Epithelial Cbfb deficiency resulted in decrease in the size of the SMG and in the saliva secretion on postnatal day 35. The Cbfb mutant SMG specifically exhibited involution of the granular convoluted tubules (GCT), with a down-regulated expression of its marker genes, such as Klk1, Ngf, and Egf. The induction of GCT is under the control of androgens, and the Cbfb mutant SMG demonstrated down-regulated expression of Crisp3, an androgen-dependent transcript. Because the circulating testosterone or tissue dihydrotestosterone levels were not affected in the Cbfb mutants, it appears that Runx/Cbfb signaling regulate androgen receptor pathway, but does not affect the circulating testosterone levels or the enzymatic conversion to DHT.
  
  
  CONCLUSIONS
  Runx signaling is important in the postnatal development of androgen-dependent GCT in the SMG.
authors.affiliation: Department of Orthodontics, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Itoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yanagita
authors.forename: Kumi
authors.initials: K
authors.lastname: Sumiyoshi
authors.forename: Satoru
authors.initials: S
authors.lastname: Hayano
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Kuremoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurosaka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Honjo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamioka
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sakai
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashiro
mesh_terms: D000818:Animals; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism*; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013363:Submandibular Gland / Q000166:cytology / Q000196:embryology*
chemical_list: C493693:Cbfb protein, mouse; D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit; C489927:Crisp3 protein, mouse; D011944:Receptors, Androgen; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor
keywords: Cbfb; craniofacial; gland; organogenesis