The Notch signaling pathway controls the size of the ocular lens by directly suppressing p57Kip2 expression.
The size of an organ must be tightly controlled so that it fits within an organism. The mammalian lens is a relatively simple organ composed of terminally differentiated, amitotic lens fiber cells capped on the anterior surface by a layer of immature, mitotic epithelial cells. The proliferation of lens epithelial cells fuels the growth of the lens, thus controling the size of the lens. We report that the Notch signaling pathway defines the boundary between proliferation and differentiation in the developing lens. The loss of Notch signaling results in the loss of epithelial cells to differentiation and a much smaller lens. We found that the Notch effector Herp2 is expressed in lens epithelium and directly suppresses p57Kip2 expression, providing a molecular link between Notch signaling and the cell cycle control machinery during lens development.
Jia
Junling
J
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lin
Min
M
Zhang
Lingna
L
York
J Philippe
JP
Zhang
Pumin
P
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000033:anatomy & histology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051880:Receptors, Notch; D012097:Repressor Proteins; C485778:Hey2 protein, mouse; C497571:Rbpj protein, mouse
J Med Genet. 2000 Sep;37(9):658-62
10978356
Exp Cell Res. 2007 Aug 15;313(14):3141-52
17560996
Genes Dev. 2000 Nov 1;14(21):2701-11
11069887
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13655-60
11095750
J Histochem Cytochem. 2001 Jan;49(1):1-8
11118473
Anat Embryol (Berl). 2001 Feb;203(2):77-87
11218061
Development. 2001 Feb;128(4):491-502
11171333
Nat Immunol. 2002 May;3(5):443-50
11967543
J Cell Physiol. 2003 Mar;194(3):237-55
12548545
Curr Biol. 2003 Feb 18;13(4):333-8
12593800
Development. 2004 Mar;131(5):965-73
14973298
Curr Opin Genet Dev. 2004 Oct;14(5):506-12
15380241
Science. 1995 Feb 17;267(5200):1024-7
7863329
Genes Dev. 1995 Mar 15;9(6):639-49
7729683
Genes Dev. 1995 Mar 15;9(6):650-62
7729684
Nature. 1995 Sep 28;377(6547):355-8
7566092
Genes Dev. 1995 Nov 1;9(21):2598-608
7590238
Genes Dev. 1995 Nov 1;9(21):2609-22
7590239
Mol Cell Neurosci. 1996;8(1):14-27
8923452
J Neurosci. 1997 Feb 15;17(4):1425-34
9006984
Nature. 1997 May 8;387(6629):151-8
9144284
Development. 1997 Oct;124(20):4133-41
9374409
Curr Top Microbiol Immunol. 1998;228:273-324
9401210
Genes Dev. 1998 Aug 1;12(15):2269-77
9694793
Genes Dev. 1998 Oct 15;12(20):3162-7
9784491
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):23-8
9874765
Nat Genet. 1999 Jan;21(1):70-1
9916792
Hum Mol Genet. 1999 May;8(5):723-30
10196361
Dev Biol. 2005 Apr 1;280(1):1-14
15766743
Mol Cell Biol. 2005 May;25(10):4262-71
15870295
J Exp Med. 2005 Jul 4;202(1):157-68
15998794
Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89
16921404
Thromb Haemost. 2006 Sep;96(3):361-70
16953280
Dev Biol. 2006 Oct 1;298(1):22-31
16899237