E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells.
Many adult stem cells reside in a special microenvironment known as the niche, where they receive essential signals that specify stem cell identity. Cell-cell adhesion mediated by cadherin and integrin plays a crucial role in maintaining stem cells within the niche. In Drosophila melanogaster, male germline stem cells (GSCs) are attached to niche component cells (i.e., the hub) via adherens junctions. The GSC centrosomes and spindle are oriented toward the hub-GSC junction, where E-cadherin-based adherens junctions are highly concentrated. For this reason, adherens junctions are thought to provide a polarity cue for GSCs to enable proper orientation of centrosomes and spindles, a critical step toward asymmetric stem cell division. However, understanding the role of E-cadherin in GSC polarity has been challenging, since GSCs carrying E-cadherin mutations are not maintained in the niche. Here, we tested whether E-cadherin is required for GSC polarity by expressing a dominant-negative form of E-cadherin. We found that E-cadherin is indeed required for polarizing GSCs toward the hub cells, an effect that may be mediated by Apc2. We also demonstrated that E-cadherin is required for the GSC centrosome orientation checkpoint, which prevents mitosis when centrosomes are not correctly oriented. We propose that E-cadherin orchestrates multiple aspects of stem cell behavior, including polarization of stem cells toward the stem cell-niche interface and adhesion of stem cells to the niche supporting cells.
Inaba
Mayu
M
Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
Yuan
Hebao
H
Salzmann
Viktoria
V
Fuller
Margaret T
MT
Yamashita
Yukiko M
YM
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology*; D005786:Gene Expression Regulation; D008297:Male; D021381:Protein Transport; D013094:Spermatozoa / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C467323:APC2 protein, Drosophila; D015820:Cadherins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins
J Cell Biol. 1999 Sep 20;146(6):1303-18
10491393
Nature. 2001 Jan 25;409(6819):522-5
11206549
Curr Biol. 2001 Jan 23;11(2):116-20
11231128
Science. 2003 Sep 12;301(5639):1547-50
12970569
J Cell Sci. 2009 Apr 1;122(Pt 7):905-11
19258396
Nature. 2005 Sep 8;437(7056):275-80
16094321
Dev Biol. 1997 Sep 1;189(1):79-94
9281339
Development. 2002 Apr;129(7):1751-62
11923210
Cell. 2008 Feb 22;132(4):598-611
18295578
Curr Opin Cell Biol. 2009 Oct;21(5):623-9
19535237
Curr Opin Cell Biol. 2009 Dec;21(6):785-95
19846287
Curr Biol. 1999 Aug 26;9(16):889-98
10469591
J Cell Sci. 2010 May 15;123(Pt 10):1613-22
20445012
Nature. 2008 Aug 28;454(7208):1132-6
18641633
Science. 2002 Jun 7;296(5574):1855-7
12052957
Dev Biol. 2002 Oct 1;250(1):71-90
12297097
Development. 1999 Jul;126(13):2829-39
10357928
Dev Biol. 2002 Oct 1;250(1):91-100
12297098
Nature. 2008 Dec 4;456(7222):599-604
18923395
Dev Biol. 1999 Dec 1;216(1):406-22
10588889
Development. 2006 Feb;133(3):529-36
16396904
Development. 2006 Sep;133(17):3283-93
16887833
Curr Biol. 1998 Feb 12;8(4):243-6
9501989
Curr Biol. 2002 Jan 22;12(2):95-104
11818059
Science. 2007 Apr 20;316(5823):402-4
17446390
Nat Cell Biol. 2001 Oct;3(10):933-8
11584277
J Cell Biol. 2009 Jun 1;185(5):779-86
19487453
Mol Biol Cell. 2009 Aug;20(16):3740-50
19553471
Cell Stem Cell. 2008 Jan 10;2(1):39-49
18371420
PLoS Biol. 2009 Aug;7(8):e1000176
19688041