Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium

被引:214
作者
Daniely, Y
Liao, G
Dixon, D
Linnoila, RI
Lori, A
Randell, SH
Oren, M
Jetten, AM
机构
[1] NIEHS, Cell Biol Sect, Div Intramural Res, Res Triangle Pk, NC 27709 USA
[2] NIEHS, Pathol Lab, Res Triangle Pk, NC 27709 USA
[3] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA
[4] NCI, Expt Pathol Sect, Cell & Canc Biol Branch, Rockville, MD 20850 USA
[5] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2004年 / 287卷 / 01期
关键词
retinoic acid; stem cell; carcinoma; basal cell; differentiation;
D O I
10.1152/ajpcell.00226.2003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The trachea and esophagus originate from the foregut endoderm during early embryonic development. Their epithelia undergo a series of changes involving the differentiation of stem cells into unique cell types and ultimately forming the mature epithelia. In this study, we monitored the expression of p63 in the esophagus and the trachea during development and examined in detail morphogenesis in p63(-/-) mice. At embryonic day 15.5 (E15.5), the esophageal and tracheobronchial epithelia contain two to three layers of cells; however, only the progenitor cells express p63. These progenitor cells differentiate first into ciliated cells (p63(-)/beta-tubulin IV+) and after birth into mature basal cells (p63(+)/K14(+)/K5(+)/BS-I-B4(+)). In the adult pseudostratified, columnar tracheal epithelium, K14(+)/K5(+)/BS-I-B4(+) basal cells stain most intensely for p63, whereas ciliated and mucosecretory cells are negative. In stratified squamous esophageal epithelium and during squamous metaplasia in the trachea, cells in the basal layer stain strongest for p63, whereas p63 staining declines progressively in transient amplifying and squamous differentiated cells. Generally, p63 expression is restricted to human squamous cell carcinomas, and adenocarcinomas and Barrett's metaplasia do not stain for p63. Examination of morphogenesis in newborn p63(-/-) mice showed an abnormal persistence of ciliated cells in the esophagus. Significantly, in both tissues, lack of p63 expression results in the development of a highly ordered, columnar ciliated epithelium deficient in basal cells. These observations indicate that p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells.
引用
收藏
页码:C171 / C181
页数:11
相关论文
共 71 条
[1]   Zebrafish ΔNp63 is a direct target of bmp signaling and encodes a transcriptional repressor blocking neural specification in the ventral ectoderm [J].
Bakkers, J ;
Hild, M ;
Kramer, C ;
Furutani-Seiki, M ;
Hammerschmidt, M .
DEVELOPMENTAL CELL, 2002, 2 (05) :617-627
[2]   Retinoic acid inhibits downregulation of ΔNp63α expression during terminal differentiation of human primary keratinocytes [J].
Bamberger, C ;
Pollet, D ;
Schmale, H .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (01) :133-138
[3]   p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast [J].
Barbareschi, M ;
Pecciarini, L ;
Cangi, MG ;
Macrì, E ;
Rizzo, A ;
Viale, G ;
Doglioni, C .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2001, 25 (08) :1054-1060
[4]   ΔNp63α expression is regulated by the phosphoinositide 3-kinase pathway [J].
Barbieri, CE ;
Barton, CE ;
Pietenpol, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :51408-51414
[5]   3 CLONAL TYPES OF KERATINOCYTE WITH DIFFERENT CAPACITIES FOR MULTIPLICATION [J].
BARRANDON, Y ;
GREEN, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (08) :2302-2306
[6]   The evolving concept of a stem cell: Entity or function? [J].
Blau, HM ;
Brazelton, TR ;
Weimann, JM .
CELL, 2001, 105 (07) :829-841
[7]   P63 gene mutations and human developmental syndromes [J].
Brunner, HG ;
Hamel, BCJ ;
van Bokhoven, H .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 112 (03) :284-290
[8]   Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis:: The role of ΔN-p63 [J].
Chilosi, M ;
Poletti, V ;
Murer, B ;
Lestani, M ;
Cancellieri, A ;
Montagna, L ;
Piccoli, P ;
Cangi, G ;
Semenzato, G ;
Doglioni, C .
LABORATORY INVESTIGATION, 2002, 82 (10) :1335-1345
[9]  
Chilosi M, 2001, SARCOIDOSIS VASC DIF, V18, P23
[10]   Differential expression of p53 gene family members p63 and p73 in head and neck squamous tumorigenesis [J].
Choi, HR ;
Batsakis, JG ;
Zhan, F ;
Sturgis, E ;
Luna, MA ;
El-Naggar, AK .
HUMAN PATHOLOGY, 2002, 33 (02) :158-164