Document Detail


p21, an important mediator of quiescence during pituitary tumor formation, is dispensable for normal pituitary development during embryogenesis.
MedLine Citation:
PMID:  22154697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A delicate balance between proliferation and differentiation must be maintained in the developing pituitary to ensure the formation of the appropriate number of hormone producing cells. In the adult, proliferation is actively restrained to prevent tumor formation. The cyclin dependent kinase inhibitors (CDKIs) of the CIP/KIP family, p21, p27 and p57, mediate cell cycle inhibition. Although p21 is induced in the pituitary upon loss of Notch signaling or initiation of tumor formation to halt cell cycle progression, its role in normal pituitary organogenesis has not been explored. In wildtype pituitaries, expression of p21 is limited to a subset of cells embryonically as well as during the postnatal proliferative phase. Mice lacking p21 do not have altered cell proliferation during early embryogenesis, but do show a slight delay in separation of proliferating progenitors from the oral ectoderm. By embryonic day 16.5, p21 mutants have an alteration in the spatial distribution of proliferating pituitary progenitors, however there is no overall change in proliferation. At postnatal day 21, there appears to be no change in proliferation, as assessed by cells expressing Ki67 protein. However, p21 mutant pituitaries have significantly less mRNA of Myc and the cyclins Ccnb1, Ccnd1, Ccnd2 and Ccne1 than wildtype pituitaries. Interestingly, unlike the redundant role in cell cycle inhibition uncovered in p27/p57 double mutants, the pituitary of p21/p27 double mutants has a similar proliferation profile to p27 single mutants at the time points examined. Taken together, these studies demonstrate that unlike p27 or p57, p21 does not play a major role in control of progenitor proliferation in the developing pituitary. However, p21 may be required to maintain normal levels of cell cycle components.
Authors:
Pamela Monahan; Ashley D Himes; Agata Parfieniuk; Lori T Raetzman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-01
Journal Detail:
Title:  Mechanisms of development     Volume:  128     ISSN:  1872-6356     ISO Abbreviation:  Mech. Dev.     Publication Date:    2012 Jan-Feb
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-05     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9101218     Medline TA:  Mech Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  640-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / genetics,  metabolism
Cell Proliferation
Cell Shape
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism*
Cyclin-Dependent Kinase Inhibitor p27 / genetics,  metabolism
Female
Gene Expression Regulation, Developmental
Ki-67 Antigen / genetics,  metabolism
Male
Mice
Mice, Knockout
Pituitary Gland / cytology,  embryology*,  metabolism
Stem Cells / metabolism,  physiology
Grant Support
ID/Acronym/Agency:
R01 DK076647/DK/NIDDK NIH HHS; R01 DK076647-04/DK/NIDDK NIH HHS; R01 DK076647-05/DK/NIDDK NIH HHS; R01DK076647/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Ki-67 Antigen; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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