title: ErbB4, a receptor tyrosine kinase, coordinates organization of the seminiferous tubules in the developing testis.
abstract: Although close to every fifth couple nowadays has difficulty conceiving, the molecular mechanisms behind the decline in human reproduction remain poorly understood. We report here that the receptor tyrosine kinase Erbb4 is a candidate causal gene, because it is expressed in a sexually dimorphic manner and is abundant in the developing and adult testes in the mouse. Sertoli cell-specific Erbb4-knockout mice have a compromised 3-dimensional organization of the testicular seminiferous tubules that affects their fertility. More specifically, adhesion defects are observed in the absence of Erbb4, which are characterized by changes in the expression of laminin-1, N-cadherin, claudin-3, and certain cell-cell junction components between the Sertoli and germ cells. Interestingly, Erbb4 knockout also had an effect on the Leydig cells, which suggests a paracrine influence of Sertoli cells expressing ErbB4. Many of the defects observed in Erbb4-knockout mice are rescued in targeted ERBB4 gain-of-function mice, pointing to a coordination role for ErbB4 in the developing testis. Thus, the ErbB4 receptor tyrosine kinase promotes seminiferous tubule development by controlling Sertoli cell and germ cell adhesion.
authors: Oulu Centre for Cell-Matrix Research (F.N., S.J.V.), Biocenter Oulu, Infotech Oulu, Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, University of Oulu, FI-90220 Oulu, Finland; Department of Medical Biochemistry and Genetics (V.V., K.E.), and Medicity Research Laboratory, University of Turku, FI-20520 Turku, Finland; Electron Microscopy Unit (I.M.), FI-90220 Oulu, Finland; Laboratory Animal Center (P.S.), University of Helsinki, FIN-00014 Helsinki, Finland; Department of Physiology (M.P.), Turku University Hospital, FI-2001 4 Turku, Finland; and Department of Oncology (K.E.), Turku University Hospital, FI-20520 Turku, Finland.
authors: Florence
authors: F
authors: Naillat
authors: Ville
authors: V
authors: Veikkolainen
authors: Ilkka
authors: I
authors: Miinalainen
authors: Petra
authors: P
authors: Sipilä
authors: Matti
authors: M
authors: Poutanen
authors: Klaus
authors: K
authors: Elenius
authors: Seppo J
authors: SJ
authors: Vainio
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D066247:Receptor, ErbB-4 / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000196:embryology* / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000196:embryology* / Q000378:metabolism
chemical_list: C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4