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Regulation of Pituitary Progenitor Differentiation by β-Catenin.

Endocrinology | 2018

The pituitary gland is a critical organ that is necessary for many physiological processes, including growth, reproduction, and stress response. The secretion of pituitary hormones from specific cell types regulates these essential processes. Pituitary hormone cell types arise from a common pool of pituitary progenitors, and mutations that disrupt the formation and differentiation of pituitary progenitors result in hypopituitarism. Canonical WNT signaling through CTNNB1 (β-catenin) is known to regulate the formation of the POU1F1 lineage of pituitary cell types. When β-catenin is deleted during the initial formation of the pituitary progenitors, Pou1f1 is not transcribed, which leads to the loss of the POU1F1 lineage. However, when β-catenin is deleted after lineage specification, there is no observable effect. Similarly, the generation of a β-catenin gain-of-function allele in early pituitary progenitors or stem cells results in the formation of craniopharyngiomas, whereas stimulating β-catenin in differentiated cell types has no effect. PROP1 is a pituitary-specific transcription factor, and the peak of PROP1 expression coincides with a critical time point in pituitary organogenesis-that is, after pituitary progenitor formation but before lineage specification. We used a Prop1-cre to conduct both loss- and gain-of-function studies on β-catenin during this critical time point. Our results demonstrate that pituitary progenitors remain sensitive to both loss and gain of β-catenin at this time point, and that either manipulation results in hypopituitarism.

Pubmed ID: 30085028 RIS Download

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Rabbit anti-Rat TSHβ (antibody)

RRID:AB_2665563

This polyclonal targets TSHβ

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Anti-TBX19 (antibody)

RRID:AB_2728662

This polyclonal targets TBX19

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Anti-SOX9 antibody (antibody)

RRID:AB_2728660

This monoclonal targets SOX9

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SOX2 Polyclonal Antibody (antibody)

RRID:AB_2716820

This polyclonal targets SOX2

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Anti-PROP1 (antibody)

RRID:AB_2728661

This polyclonal targets PROP1

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anti Pit-1 (antibody)

RRID:AB_2722652

This polyclonal targets PIT1/POU1F1

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Rabbit anti-Human ACTH (antibody)

RRID:AB_2665562

This polyclonal targets POMC

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Notch2 (antibody)

RRID:AB_2153638

This monoclonal targets NOTCH2

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Guinea Pig anti-Rat LHβ (antibody)

RRID:AB_2665565

This polyclonal targets LHβ

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Lim 3 (antibody)

RRID:AB_2135805

This monoclonal targets LHX3

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LEF-1 (N-17) (antibody)

RRID:AB_2135616

This polyclonal targets LEF1

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Ki67 antibody - Proliferation Marker (antibody)

RRID:AB_443209

This polyclonal targets Ki67 antibody - Proliferation Marker

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Monkey anti-Rat GH (antibody)

RRID:AB_2665564

This polyclonal targets GH

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GFP-avictoria (antibody)

RRID:AB_303395

This polyclonal targets GFP

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Anti-Cytokeratin 8+18 antibody (antibody)

RRID:AB_2728659

This polyclonal targets Cytokeratin 8+18

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cyclin D2 (M-20) (antibody)

RRID:AB_2070794

This monoclonal targets Raised against peptide corresponding to an AA sequence at the C-terminus of mouse origin

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