Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo.
The axis of asymmetric cell division is controlled to determine the future position of differentiated cells during animal development. The asymmetric localization of PAR proteins in the Drosophila neuroblast and C. elegans embryo are aligned with the axes of the embryo. However, whether extracellular or intracellular signals determine the orientation of the localization of PAR proteins remains controversial. In C. elegans, the P0 zygote and germline cells (P1, P2, and P3) undergo a series of asymmetric cell divisions. Interestingly, the axis of the P0 and P1 divisions is opposite to that of the P2 and P3 divisions. PAR-2, a ring-finger protein, and PAR-1, a kinase, relocalize to the anterior side of the P2 and P3 germline precursors at the site of contact with endodermal precursors. Using an in vitro method, we have found that the PAR-2 protein is distributed asymmetrically in the absence of extracellular signals, but the orientation of the protein localization in the P2 and P3 cells is determined by contact with endodermal precursor cells. Our mutant analyses suggest that mes-1 and src-1, which respectively encode a transmembrane protein and a tyrosine kinase, were not required to establish the asymmetric distribution of PAR-2, but were required to determine its orientation at the site of contact with the endodermal precursors. The PAR-2 localization during the asymmetric P2 and P3 divisions is controlled by extracellular signals via MES-1/SRC-1 signaling. Our findings suggest that Src functions as an evolutionarily conserved molecular link that coordinates extrinsic cues with PAR protein localization.
Arata
Yukinobu
Y
Laboratory for Cell Fate Decision, RIKEN, Center for Developmental Biology, Kobe, Japan. arata@riken.jp
Lee
Jen-Yi
JY
Goldstein
Bob
B
Sawa
Hitoshi
H
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D005110:Extracellular Space / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C415743:Mes-1 protein, C elegans; C087977:par-2 protein, C elegans; D011494:Protein Kinases; C471235:SRC-1 protein, C elegans
Development. 2003 Jan;130(2):307-20
12466198
Development. 2000 Oct;127(20):4419-31
11003841
Development. 2005 Dec;132(23):5161-72
16251208
Dev Biol. 1987 Aug;122(2):452-63
3596018
Development. 1996 Jul;122(7):2043-50
8681785
J Neurochem. 2004 Apr;89(1):109-18
15030394
Development. 1995 Sep;121(9):2961-72
7555722
Development. 1995 Apr;121(4):1227-36
7743934
Curr Biol. 2004 May 25;14(10):851-62
15186741
Dev Cell. 2003 Mar;4(3):287-8
12636908
Methods Cell Biol. 1995;48:303-21
8531731
Development. 1996 May;122(5):1467-74
8625834
Science. 2007 Mar 23;315(5819):1687-91
17332376
Biochim Biophys Acta. 2010 Feb;1803(2):183-90
18977250
J Immunol. 2009 Jul 15;183(2):1215-21
19553522
Immunity. 2005 Jun;22(6):737-48
15963788
Dev Biol. 1983 Mar;96(1):189-96
6825952
Cell. 1995 May 19;81(4):611-20
7758115
Nature. 2004 Sep 2;431(7004):92-6
15343338
Development. 2007 Mar;134(6):1035-43
17287245
Dev Cell. 2002 Jul;3(1):113-25
12110172
Nat Cell Biol. 2003 Apr;5(4):267-70
12669070
Nat Rev Immunol. 2003 Dec;3(12):973-83
14647479
Nature. 1998 Feb 19;391(6669):806-11
9486653
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14976-81
17848508
J Cell Biol. 2010 Mar 8;188(5):693-706
20194641
J Cell Biol. 1995 May;129(4):1071-80
7744956
Int Rev Cell Mol Biol. 2009;274:129-82
19349037
Development. 2006 Feb;133(3):529-36
16396904
Development. 1996 Oct;122(10):3075-84
8898221
Curr Opin Neurobiol. 2008 Feb;18(1):4-11
18513950