title: Suppression of β1-integrin in gonadotropin-releasing hormone cells disrupts migration and axonal extension resulting in severe reproductive alterations.
abstract: Reproduction in mammals is dependent on the function of hypothalamic neurons whose axons project to the hypothalamic median eminence (ME) where they release gonadotropin-releasing hormone (GnRH) into a specialized capillary network for delivery to the anterior pituitary. These neurons originate prenatally in the nasal placode and migrate into the forebrain along the olfactory-vomeronasal nerves. The complex developmental events leading to the correct establishment of the GnRH system are tightly regulated by the specific spatiotemporal expression patterns of guidance cues and extracellular matrix molecules, the functions of which, in part, are mediated by their binding to β1-subunit-containing integrins. To determine the biological role of these cell-surface proteins in reproduction, Cre/LoxP technology was used to generate GnRH neuron-specific β1-integrin conditional KO (GnRH-Itgb1(-/-)) mice. Loss of β1-integrin signaling impaired migration of GnRH neurons, their axonal extension to the ME, timing of pubertal onset, and fertility in these mice. These results identify β1-integrin as a gene involved in normal development of the GnRH system and demonstrate a fundamental role for this protein in acquisition of normal reproductive competence in female mice.
authors.affiliation: Inserm U837, Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, France.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Parkash
authors.forename: Irene
authors.initials: I
authors.lastname: Cimino
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ferraris
authors.forename: Filippo
authors.initials: F
authors.lastname: Casoni
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
authors.forename: Hélène
authors.initials: H
authors.lastname: Cappy
authors.forename: Vincent
authors.initials: V
authors.lastname: Prevot
authors.forename: Paolo
authors.initials: P
authors.lastname: Giacobini
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology; D004247:DNA / Q000235:genetics; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000235:genetics* / Q000503:physiopathology; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D007986:Luteinizing Hormone / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D010053:Ovary / Q000473:pathology; D016133:Polymerase Chain Reaction; D012741:Sexual Maturation / Q000235:genetics / Q000502:physiology
chemical_list: D019012:Integrin beta1; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D004247:DNA