title: The long noncoding RNA Neat1 is required for mammary gland development and lactation.
abstract: The lncRNA Neat1 is an essential architectural component of paraspeckle nuclear bodies. Although cell-based studies identified Neat1-paraspeckles as key regulators of gene expression through retention of hyperdited mRNAs and/or transcription factors, it is unclear under which specific physiological conditions paraspeckles are formed in vivo and whether they have any biological relevance. Herein, we show that paraspeckles are assembled in luminal epithelial cells during mammary gland development. Importantly, genetic ablation of Neat1 results in aberrant mammary gland morphogenesis and lactation defects. We provide evidence that the lactation defect is caused by a decreased ability of Neat1-mutant cells to sustain high rates of proliferation during lobular-alveolar development. This study is the first to assign an important biological function to the lncRNA Neat1 and to link it to the presence of paraspeckles nuclear bodies in vivo.
authors.affiliation: Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Standaert
authors.affiliation: Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium.
authors.forename: Carmen
authors.initials: C
authors.lastname: Adriaens
authors.affiliation: Center for the Biology of Disease, Histopathology Lab, VIB, Leuven 3000, Belgium Center for Human Genetics, Histopathology Lab, KULeuven, Leuven 3000, Belgium.
authors.forename: Enrico
authors.initials: E
authors.lastname: Radaelli
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Van Keymeulen
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Cedric
authors.initials: C
authors.lastname: Blanpain
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
authors.affiliation: RNA Biology Laboratory, RIKEN, Saitama 351-0198, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, VIB, Leuven 3000, Belgium Center for Human Genetics, Laboratory for Molecular Cancer Biology, KULeuven, Leuven 3000, Belgium jeanchristophe.marine@cme.vib-kuleuven.be.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C577275:NEAT1 long non-coding RNA, mouse; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: NEAT1; long noncoding RNA; mammary gland development; paraspeckles