title: Notch signaling in postnatal pituitary expansion: proliferation, progenitors, and cell specification.
abstract: Mutations in PROP1 account for up to half of the cases of combined pituitary hormone deficiency that result from known causes. Despite this, few signaling molecules and pathways that influence PROP1 expression have been identified. Notch signaling has been linked to Prop1 expression, but the developmental periods during which Notch signaling influences Prop1 and overall pituitary development remain unclear. To test the requirement for Notch signaling in establishing the normal pituitary hormone milieu, we generated mice with early embryonic conditional loss of Notch2 (conditional knockout) and examined the consequences of chemical Notch inhibition during early postnatal pituitary maturation. We show that loss of Notch2 has little influence on early embryonic pituitary proliferation but is crucial for postnatal progenitor maintenance and proliferation. In addition, we show that Notch signaling is necessary embryonically and postnatally for Prop1 expression and robust Pit1 lineage hormone cell expansion, as well as repression of the corticotrope lineage. Taken together, our studies identify temporal and cell type-specific roles for Notch signaling and highlight the importance of this pathway throughout pituitary development.
authors.affiliation: Department of Molecular and Integrative Physiology (L.B.N., A.D.H., D.R.G., L.T.R.) and Neuroscience Program (L.T.R.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801.
authors.forename: Leah B
authors.initials: LB
authors.lastname: Nantie
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Himes
authors.forename: Dan R
authors.initials: DR
authors.lastname: Getz
authors.forename: Lori T
authors.initials: LT
authors.lastname: Raetzman
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D052680:Corticotrophs / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000502:physiology*; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000166:cytology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051883:Receptor, Notch2 / Q000502:physiology*; D015398:Signal Transduction; D037322:Thyrotropin, beta Subunit / Q000378:metabolism; D046509:Tissue Culture Techniques; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D013006:Growth Hormone; D011333:Pro-Opiomelanocortin; D051883:Receptor, Notch2; D037322:Thyrotropin, beta Subunit; D050817:Transcription Factor Pit-1; C497765:Notch2 protein, mouse; C494185:Pou1f1 protein, mouse