Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

REFERENCES

Adam
J.
,
Myat
A.
,
Le Roux
I.
,
Eddison
M.
,
Henrique
D.
,
Ish-Horowicz
D.
,
Lewis
J.
(
1998
)
Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development.
Development
125
,
4645
4654
Appel
B.
,
Eisen
J. S.
(
1998
)
Regulation of neuronal specification in the zebrafish spinal cord by Delta function.
Development
125
,
371
380
Artavanis-Tsakonas
S.
,
Matsuno
K.
,
Fortini
M. E.
(
1995
)
Notch signalling.
Science
267
,
225
232
Becerra
M.
,
Anadon
R.
(
1993
)
Development of the inner ear of the brown trout (Salmo trutta fario): I. Gross morphology and sensory cell proliferation.
J. Morphol
216
,
209
223
Chitnis
A.
,
Henrique
D.
,
Lewis
J.
,
Ish-Horowicz
D.
,
Kintner
C.
(
1995
)
Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta.
Nature
375
,
761
766
Chitnis
A. B.
(
1995
)
The role of Notch in lateral inhibition and cell fate specification.
Mol. Cell. Neurosci
6
,
311
321
Collier
J. R.
,
Monk
N. A. M.
,
Maini
P. K.
,
Lewis
J. H.
(
1996
)
Pattern formation by lateral inhibition with feedback: a mathematical model of Delta-Notch intercellular signalling.
J. Theor. Biol
183
,
429
446
Conlon
R. A.
,
Reaume
A. G.
,
Rossant
J.
(
1995
)
Notch1 is required for the coordinate segmentation of somites.
Development
121
,
1533
1545
Corwin
J. T.
,
Jones
J. E.
,
Katayama
A.
,
Kelley
M. W.
,
Warchol
M. E.
(
1991
)
Hair cell regeneration: the identities of progenitor cells, potential triggers and instructive cues.
Ciba Found. Symp
160
,
103
130
Dornseifer
P.
,
Takke
C.
,
Campos-Ortega
J. A.
(
1997
)
Overexpression of a zebrafish homologue of the Drosophila neurogenic gene Delta perturbs differentiation of primary neurons and somite development.
Mech. Dev
63
,
159
171
Fermin
C. D.
,
Igarashi
M.
(
1986
)
Review of statoconia formation in birds and original research in chicks (Gallus domesticus).
Scan. Electron Microsc
4
,
1649
1665
Ghysen
A.
,
Dambly-Chaudiere
C.
,
Jan
L. Y.
,
Jan
Y.-N.
(
1993
)
Cell interactions and gene interactions in peripheral neurogenesis.
Genes Dev
7
,
723
733
Goodyear
R.
,
Richardson
G.
(
1997
)
Pattern formation in the basilar papilla: evidence for cell rearrangement.
J. Neurosci
17
,
6289
6301
Gridley
T.
(
1997
)
Notch signaling in vertebrate development and disease.
Mol. Cell. Neurosci
9
,
103
8
Guo
M.
,
Jan
L. Y.
,
Jan
Y. N.
(
1996
)
Control of daughter cell fates during asymmetric division: interaction of Numb and Notch.
Neuron
17
,
27
41
Haddon
C.
,
Lewis
J.
(
1996
)
Early ear development in the embryo of the zebrafish, Danio rerio.
J. Comp. Neurol
365
,
113
128
Haddon
C.
,
Smithers
L.
,
Schneider-Maunoury
S.
,
Coche
T.
,
Henrique
D.
,
Lewis
J.
(
1998
)
Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis.
Development
125
,
359
370
Hammerschmidt
M.
,
Nusslein-Volhard
C.
(
1993
)
The expression of a zebrafish gene homolgous to Drosophila snail suggests a conserved function in invertebrate and vertebrate gastrulation.
Development
119
,
1107
1118
Hartenstein
V.
,
Posakony
J. W.
(
1990
)
A dual function of the Notch gene in Drosophila sensillum development.
Dev. Biol
142
,
13
–.
Hayashi
H.
,
Mochii
M.
,
Kodama
R.
,
Hamada
Y.
,
Mizuno
N.
,
Eguchi
G.
,
Tachi
C.
(
1996
)
Isolation of a novel chick homolog of Serrate and its coexpression with C-Notch-1 in chick development.
Int. J. Dev. Biol
40
,
1089
1096
Heitzler
P.
,
Simpson
P.
(
1991
)
The choice of cell fate in the epidermis of Drosophila.
Cell
64
,
1083
1092
Henrique
D.
,
Adam
J.
,
Myat
A.
,
Chitnis
A.
,
Lewis
J.
,
Ish-Horowicz
D.
(
1995
)
Expression of a Delta homologue in prospective neurons in the chick.
Nature
375
,
787
790
Henrique
D.
,
Hirsinger
E.
,
Adam
J.
,
Le Roux
I.
,
Pourquie
O.
,
Ish-Horowicz
D.
,
Lewis
J.
(
1997
)
Maintenance of neuroepithelial progenitor cells by Delta-Notch signaling in the embryonic chick retina.
Curr. Biol
7
,
661
670
Hrabe de Angelis
M.
,
McIntyre
J.
,
Gossler
A.
(
1997
)
Maintenance of somite borders in mice requires the Delta homologue DII1.
Nature
386
,
717
721
Jan
Y. N.
,
Jan
L. Y.
(
1995
)
Maggot's hair and bug's eye: role of cell interactions and intrinsic factors in cell fate specification.
Neuron
14
,
1
5
Jen
W. C.
,
Wettstein
D.
,
Turner
D.
,
Chitnis
A.
,
Kintner
C.
(
1997
)
The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos.
Development
124
,
1169
1178
Jiang
Y.-J.
,
Brand
M.
,
Heisenberg
C.-P.
,
Beuchle
D.
,
Furutani-Seiki
M.
,
Kelsh
R. N.
,
Warga
R. M.
,
Granato
M.
,
Haffter
P.
,
Hammerschmidt
M.
, et al. 
(
1996
)
Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio.
Development
123
,
205
216
Jones
J. E.
,
Corwin
J. T.
(
1996
)
Regeneration of sensory cells after laser ablation in the lateral line system: hair cell lineage and macrophage behavior revealed by time-lapse video microscopy.
J Neurosci
16
,
649
62
Kimmel
C. B.
,
Ballard
W. W.
,
Kimmel
S. R.
,
Ullmann
B.
,
Schilling
T. F.
(
1995
)
Stages of embryonic development of the zebrafish.
Dev. Dyn
203
,
253
310
Korzh
V.
,
Edlund
T.
,
Thor
S.
(
1993
)
Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation.
Development
118
,
417
425
Lewis
J.
(
1996
)
Neurogenic genes and vertebrate neurogenesis.
Curr. Opin. Neurobiol
6
,
3
10
Lindsell
C. E.
,
Boulter
J.
,
diSibio
G.
,
Gossler
A.
,
Weinmaster
G.
(
1996
)
Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development.
Mol. Cell. Neurosci
8
,
14
27
Malicki
J.
,
Schier
A. F.
,
Solnica-Krezel
L.
,
Stemple
D. L.
,
Neuhauss
S. C. F.
,
Stainier
D. Y. R.
,
Abdelilah
S.
,
Rangini
Z.
,
Zwartkruis
F.
,
Driever
W.
(
1996
)
Mutations affecting development of the zebrafish ear.
Development
123
,
275
283
Muskavitch
M. A.
(
1994
)
Delta-Notch signaling and Drosophila cell fate choice.
Dev. Biol
166
,
415
430
Myat
A.
,
Henrique
D.
,
Ish-Horowicz
D.
,
Lewis
J.
(
1996
)
A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis.
Dev. Biol
174
,
233
247
Oh
S. H.
,
Johnson
R.
,
Wu
D. K.
(
1996
)
Differential expression of bone morphogenetic proteins in the developing vestibular and auditory sensory organs.
J. Neurosci
16
,
6463
6475
Oxtoby
E.
,
Jowett
T.
(
1993
)
Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development.
Nucleic Acids Res
21
,
1087
1095
Parks
A. L.
,
Muskavitch
M. A.
(
1993
)
Delta function is required for bristle organ determination and morphogenesis in Drosophila.
Dev. Biol
157
,
484
496
Platt
C.
(
1993
)
Zebrafish inner ear sensory surfaces are similar to those in goldfish.
Hearing Res
65
,
133
140
Riley
B. B.
,
Grunwald
D. J.
(
1996
)
A mutation in zebrafish affecting a localized cellular function required for normal ear development.
Dev. Biol
179
,
427
435
Riley
B. B.
,
Zhu
C.
,
Janetopoulos
C.
,
Aufderheide
K. J.
(
1997
)
A critical period of ear development controlled by distinct populations of ciliated cells in the zebrafish.
Dev Biol
191
,
191
201
Schier
A. F.
,
Neuhauss
S. C. F.
,
Harvey
M.
,
Malicki
J.
,
Solnica-Krezel
L.
,
Stainier
D. Y. R.
,
Zwartkruis
F.
,
Abdelilah
S.
,
Stemple
D. L.
,
Rangini
Z.
,
Yang
H.
,
Driever
W.
(
1996
)
Mutations affecting the development of the embryonic zebrafish brain.
Development
123
,
165
178
Sternberg
P. W.
(
1993
)
Falling off the knife edge.
Curr. Biol
3
,
763
765
Stone
J. S.
,
Cotanche
D. A.
(
1994
)
Identification of the timing of S phase and the patterns of cell proliferation during hair cell regeneration in the chick cochlea.
J. Comp. Neurol
341
,
50
67
Strähle
U.
,
Blader
P.
,
Adam
J.
,
Ingham
P. W.
(
1994
)
A simple and efficient procedure for non-isotopic in situ hybridisation to sectioned material.
Trends Genet
10
,
75
76
Takemura
T.
,
Sakagami
M.
,
Takebayashi
K.
,
Umemoto
M.
,
Nakase
T.
,
Takaoka
K.
,
Kubo
T.
,
Kitamura
Y.
,
Nomura
S.
(
1996
)
Localization of bone morphogenetic protein-4 messenger-RNA in developing mouse cochlea.
Hearing Res
95
,
26
32
Weisleder
P.
,
Tsue
T. T.
,
Rubel
E. W.
(
1995
)
Hair cell replacement in avian vestibular epithelium: supporting cell to type I hair cell.
Hearing Res
82
,
125
133
Wilkinson
H. A.
,
Fitzgerald
K.
,
Greenwald
I.
(
1994
)
Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision.
Cell
79
,
1187
1198
Zeng
C.
,
Younger-Shepherd
S.
,
Jan
L. Y.
,
Jan
Y. N.
(
1998
)
Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage.
Genes Dev
12
,
1086
1091
This content is only available via PDF.