title: Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.
abstract: DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance.
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: P
authors.initials: P
authors.lastname: García-Gallastegui
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Luzuriaga
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Aurrekoetxea
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Baladrón
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ruiz-Hidalgo
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: García-Ramírez
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Laborda
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Unda
authors.affiliation: Department of Cell Biology and Histology. Faculty of Medicine and Dentistry, University of the Basque Country, UPV/EHU, Leioa, 48940, Bizkaia, Spain. gaskon.ibarretxe@ehu.eus.|Department of Inorganic and Organic Chemistry and Biochemistry, Medical School, Regional Center for Biomedical Research, University of Castilla-La Mancha, Calle Almansa 14, 02008, Albacete, Spain. gaskon.ibarretxe@ehu.eus.
authors.forename: G
authors.initials: G
authors.lastname: Ibarretxe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005726:Ganglia, Parasympathetic / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D053555:Keratin-5 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D012463:Saliva; D012469:Salivary Glands / Q000196:embryology / Q000294:innervation / Q000473:pathology* / Q000648:ultrastructure; D013234:Stem Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053547:Keratin-14; D053555:Keratin-5
keywords: DLK1; Mouse; Progenitor cells; Saliva; Salivary glands