Document Detail


Numb deletion in POMC-expressing cells impairs pituitary intermediate lobe cell adhesion, progenitor cell localization, and neuro-intermediate lobe boundary formation.
MedLine Citation:
PMID:  21084383     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pituitary gland contains six distinct hormone-secreting cell types that are essential for basic physiological processes including fertility and responding to stress. Formation of hormone-secreting cells during development relies on Notch signaling to prevent progenitors from prematurely differentiating. The nature of the signal curtailing Notch signaling in the pituitary is unknown, but a good candidate is the endocytic adaptor protein NUMB. NUMB targets Notch for proteolytic degradation, but it also has a broad range of actions, including stabilizing adherens junctions through interactions with cadherins and influencing cell proliferation by stabilizing expression of the tumor suppressor protein p53. Here, we show that NUMB and its closely related homolog, NUMBLIKE, are expressed in undifferentiated cells during development and later in gonadotropes in the anterior lobe and melanotropes of the intermediate lobe. All four isoforms of NUMB, are detectable in the pituitary, with the shorter forms becoming more prominent after adolescence. Conditionally deleting Numb and Numblike in the intermediate lobe melanotropes with Pomc Cre mice dramatically alters the morphology of cells in the intermediate lobe, coincident with impaired localization of adherens junctions proteins including E-CADHERIN, N-CADHERIN, β-CATENIN, and α-CATENIN. Strikingly, the border between posterior and intermediate lobes is also disrupted. These mice also have disorganized progenitor cells, marked by SOX2, but proliferation is unaffected. Unexpectedly, Notch activity appears normal in conditional knockout mice. Thus, Numb is critical for maintaining cell-cell interactions in the pituitary intermediate lobe that are essential for proper cell placement.
Authors:
Tyler B Moran; Leah B Goldberg; Sarah L Serviss; Lori T Raetzman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-17
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  25     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-04-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  117-27     Citation Subset:  IM    
Affiliation:
University of Illinois at Urbana-Champaign, 407 South Goodwin Avenue, Urbana, Illinois 61801, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion
Cell Movement*
Cell Proliferation
Gene Deletion*
Gene Expression Regulation, Developmental
Gonadotrophs / cytology,  metabolism
Integrases / metabolism
Melanotrophs / cytology,  metabolism
Membrane Proteins / genetics*,  metabolism
Mice
Mice, Knockout
Nerve Tissue Proteins / genetics*,  metabolism
Pituitary Gland, Intermediate / cytology*,  embryology*,  metabolism
Pro-Opiomelanocortin / metabolism*
Protein Isoforms / genetics,  metabolism
Receptors, Notch / metabolism
Stem Cells / cytology*,  metabolism
Grant Support
ID/Acronym/Agency:
R01DK076647/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Numb protein, mouse; 0/Numbl protein, mouse; 0/Protein Isoforms; 0/Receptors, Notch; 66796-54-1/Pro-Opiomelanocortin; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections

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