The fully linked HTML version of this article has now been published.
Development ePress online publication date 1 Sep 2005
doi: 10.1242/dev.02002
Research article
The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear
Amy E. Kiernan,
Ralf Cordes,
Raphael Kopan,
Achim Gossler,
and
Thomas Gridley*
* Author for correspondence (e-mail: gridley{at}jax.org)
The mammalian auditory sensory epithelium, the organ of Corti, contains sensory hair cells and nonsensory supporting cells arranged in a highly patterned mosaic. Notch-mediated lateral inhibition is the proposed mechanism for creating this sensory mosaic. Previous work has shown that mice lacking the Notch ligand JAG2 differentiate supernumerary hair cells in the cochlea, consistent with the lateral inhibitory model. However, it was not clear why only relatively modest increases in hair cell production were observed in Jag2 mutant mice. Here, we show that another Notch ligand, DLL1, functions synergistically with JAG2 in regulating hair cell differentiation in the cochlea. We also show by conditional inactivation that these ligands probably signal through the NOTCH1 receptor. Supernumerary hair cells in Dll1/Jag2 double mutants arise primarily through a switch in cell fate, rather than through excess proliferation. Although these results demonstrate an important role for Notch-mediated lateral inhibition during cochlear hair cell patterning, we also detected abnormally prolonged cellular proliferation that preferentially affected supporting cells in the organ of Corti. Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Dabdoub, C. Puligilla, J. M. Jones, B. Fritzsch, K. S. E. Cheah, L. H. Pevny, and M. W. Kelley
Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea
PNAS,
November 25, 2008;
105(47):
18396 - 18401.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Fein, M. A. Wright, E. A. Slat, A. B. Ribera, and L. L. Isom
scn1bb, a Zebrafish Ortholog of SCN1B Expressed in Excitable and Nonexcitable Cells, Affects Motor Neuron Axon Morphology and Touch Sensitivity
J. Neurosci.,
November 19, 2008;
28(47):
12510 - 12522.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
U.-M. Fiuza and A. M. Arias
Cell and molecular biology of Notch
J. Endocrinol.,
September 1, 2007;
194(3):
459 - 474.
[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]
|
|
|
|
|
|
|
B. E. Jacques, M. E. Montcouquiol, E. M. Layman, M. Lewandoski, and M. W. Kelley
Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea
Development,
August 15, 2007;
134(16):
3021 - 3029.
[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]
|
|
|
|
|
|
|
K.-A. Kim, J.-H. Kim, Y. Wang, and H. S. Sul
Pref-1 (Preadipocyte Factor 1) Activates the MEK/Extracellular Signal-Regulated Kinase Pathway To Inhibit Adipocyte Differentiation
Mol. Cell. Biol.,
March 15, 2007;
27(6):
2294 - 2308.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-T. Cheng, M. Kim, M. T. Valerius, K. Surendran, K. Schuster-Gossler, A. Gossler, A. P. McMahon, and R. Kopan
Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron
Development,
February 15, 2007;
134(4):
801 - 811.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
R. Brooker, K. Hozumi, and J. Lewis
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Development,
April 1, 2006;
133(7):
1277 - 1286.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
