The fully linked HTML version of this article has now been published.
Development ePress online publication date 22 Feb 2006
doi: 10.1242/dev.02284
Research article
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Rachael Brooker,
Katsuto Hozumi,
and
Julian Lewis*
* Author for correspondence (e-mail: julian.lewis{at}cancer.org.uk)
Each of the sensory patches in the epithelium of the inner ear is a mosaic of hair cells and supporting cells. Notch signalling is thought to govern this pattern of differentiation through lateral inhibition. Recent experiments in the chick suggest, however, that Notch signalling also has a prior function - inductive rather than inhibitory - in defining the prosensory patches from which the differentiated cells arise. Several Notch ligands are expressed in each patch, but their individual roles in relation to the two functions of Notch signalling are unclear. We have used a Cre-LoxP approach to knock out two of these ligands, Delta1 (Dll1) and Jagged1 (Jag1) , in the mouse ear. In the absence of Dll1, auditory hair cells develop early and in excess, in agreement with the lateral inhibition hypothesis. In the absence of Jag1, by contrast, the total number of these cells is strongly reduced, with complete loss of cochlear outer hair cells and some groups of vestibular hair cells, indicating that Jag1 is required for the prosensory inductive function of Notch. The number of cochlear inner hair cells, however, is almost doubled. This correlates with loss of expression of the cell cycle inhibitor p27Kip1 (Cdkn1b), suggesting that signalling by Jag1 is also needed to limit proliferation of prosensory cells, and that there is a core part of this population whose prosensory character is established independently of Jag1-Notch signalling. Our findings confirm that Notch signalling in the ear has distinct prosensory and lateral-inhibitory functions, for which different ligands are primarily responsible.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Zou, C. Erickson, E.-H. Kim, D. Jin, B. Fritzsch, and P.-X. Xu
Eya1 gene dosage critically affects the development of sensory epithelia in the mammalian inner ear
Hum. Mol. Genet.,
November 1, 2008;
17(21):
3340 - 3356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.-N. Tsao, F. Chen, K. I. Izvolsky, J. Walker, M. A. Kukuruzinska, J. Lu, and W. V. Cardoso
{gamma}-Secretase Activation of Notch Signaling Regulates the Balance of Proximal and Distal Fates in Progenitor Cells of the Developing Lung
J. Biol. Chem.,
October 24, 2008;
283(43):
29532 - 29544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Urs, A. Roudabush, C. F. O'Neill, I. Pinz, I. Prudovsky, D. Kacer, Y. Tang, L. Liaw, and D. Small
Soluble Forms of the Notch Ligands Delta1 and Jagged1 Promote in Vivo Tumorigenicity in NIH3T3 Fibroblasts with Distinct Phenotypes
Am. J. Pathol.,
September 1, 2008;
173(3):
865 - 878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Driver, S. P. Pryor, P. Hill, J. Turner, U. Ruther, L. G. Biesecker, A. J. Griffith, and M. W. Kelley
Hedgehog Signaling Regulates Sensory Cell Formation and Auditory Function in Mice and Humans
J. Neurosci.,
July 16, 2008;
28(29):
7350 - 7358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-M. Kwon, M. Eguchi, M. Wada, Y. Iwami, K. Hozumi, H. Iwaguro, H. Masuda, A. Kawamoto, and T. Asahara
Specific Jagged-1 Signal From Bone Marrow Microenvironment Is Required for Endothelial Progenitor Cell Development for Neovascularization
Circulation,
July 8, 2008;
118(2):
157 - 165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Jayasena, T. Ohyama, N. Segil, and A. K. Groves
Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode
Development,
July 1, 2008;
135(13):
2251 - 2261.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hayashi, C. A. Ray, and O. Bermingham-McDonogh
Fgf20 Is Required for Sensory Epithelial Specification in the Developing Cochlea
J. Neurosci.,
June 4, 2008;
28(23):
5991 - 5999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Y. Ma, E. W Rubel, and D. W. Raible
Notch Signaling Regulates the Extent of Hair Cell Regeneration in the Zebrafish Lateral Line
J. Neurosci.,
February 27, 2008;
28(9):
2261 - 2273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Raft, E. J. Koundakjian, H. Quinones, C. S. Jayasena, L. V. Goodrich, J. E. Johnson, N. Segil, and A. K. Groves
Cross-regulation of Ngn1 and Math1 coordinates the production of neurons and sensory hair cells during inner ear development
Development,
December 15, 2007;
134(24):
4405 - 4415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ahnfelt-Ronne, M. C. Jorgensen, J. Hald, O. D. Madsen, P. Serup, and J. Hecksher-Sorensen
An Improved Method for Three-dimensional Reconstruction of Protein Expression Patterns in Intact Mouse and Chicken Embryos and Organs
J. Histochem. Cytochem.,
September 1, 2007;
55(9):
925 - 930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Kiernan, R. Li, N. L. Hawes, G. A. Churchill, and T. Gridley
Genetic Background Modifies Inner Ear and Eye Phenotypes of Jag1 Heterozygous Mice
Genetics,
September 1, 2007;
177(1):
307 - 311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Daudet, L. Ariza-McNaughton, and J. Lewis
Notch signalling is needed to maintain, but not to initiate, the formation of prosensory patches in the chick inner ear
Development,
June 15, 2007;
134(12):
2369 - 2378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Hofmann and M. L. Iruela-Arispe
Notch Signaling in Blood Vessels: Who Is Talking to Whom About What?
Circ. Res.,
June 8, 2007;
100(11):
1556 - 1568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Rubio-Aliaga, D. Soewarto, S. Wagner, M. Klaften, H. Fuchs, S. Kalaydjiev, D. H. Busch, M. Klempt, B. Rathkolb, E. Wolf, et al.
A Genetic Screen for Modifiers of the Delta1-Dependent Notch Signaling Function in the Mouse
Genetics,
March 1, 2007;
175(3):
1451 - 1463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Millimaki, E. M. Sweet, M. S. Dhason, and B. B. Riley
Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch
Development,
January 15, 2007;
134(2):
295 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Estrach, C. A. Ambler, C. L. Lo Celso, K. Hozumi, and F. M. Watt
Jagged 1 is a {beta}-catenin target gene required for ectopic hair follicle formation in adult epidermis
Development,
November 15, 2006;
133(22):
4427 - 4438.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. S. Tang, H. M. Alger, and F. A. Pereira
COUP-TFI controls Notch regulation of hair cell and support cell differentiation
Development,
September 15, 2006;
133(18):
3683 - 3693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-S. Lee, F. Liu, and N. Segil
A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development
Development,
August 1, 2006;
133(15):
2817 - 2826.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
