The inner ear is induced from cranial ectoderm adjacent to the hindbrain. Despite almost a century of study, the molecular mechanisms of inner ear induction remain obscure. We have identified four genes expressed very early in the anlage of the inner ear, the otic placode. Pax-2, Sox-3, BMP-7 and Notch are all expressed in placodal ectoderm from the 4–5 somite stage (ss) onwards, well before the otic placode becomes morphologically visible at the 12–14ss. We have used these four molecular markers to show that cranial ectoderm becomes specified to form the otic placode at the 4–6ss, and that this ectoderm is committed to a placodal fate by the 10ss. We also demonstrate that much of the embryonic ectoderm is competent to generate an otic placode if taken at a sufficiently early age. We have mapped the location of otic placode-inducing activity along the rostrocaudal axis of the embryo, and have determined that this activity persists at least until the 10ss. Use of the four molecular otic placode markers suggests that induction of the otic placode in birds occurs earlier than previously thought, and proceeds in a series of steps that are independently regulated.

REFERENCES

REFERENCES
Acampora
D.
,
Merlo
G. R.
,
Paleari
L.
,
Zerega
B.
,
Postiglione
M. P.
,
Mantero
S.
,
Bober
E.
,
Barbieri
O.
,
Simeone
A.
,
Levi
G.
(
1999
)
Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5.
Development
126
,
3795
3809
Baker
C. V.
,
Stark
M. R.
,
Marcelle
C.
,
Bronner-Fraser
M.
(
1999
)
Competence, specification and induction of Pax-3 in the trigeminal placode.
Development
126
,
147
156
Bottenstein
J. E.
,
Sato
G. H.
(
1979
)
Growth of a rat neuroblastoma cell line in serum-free supplemented medium.
Proc. Natl. Acad. Sci. USA
76
,
514
517
Charrier
J. B.
,
Teillet
M. A.
,
Lapointe
F.
,
Le Douarin
N. M.
(
1999
)
Defining subregions of Hensen's node essential for caudalward movement, midline development and cell survival.
Development
126
,
4771
4783
Depew
M. J.
,
Liu
J. K.
,
Long
J. E.
,
Presley
R.
,
Meneses
J. J.
,
Pedersen
R. A.
,
Rubenstein
J. L.
(
1999
)
Dlx5 regulates regional development of the branchial arches and sensory capsules.
Development
126
,
3831
3846
Detwiler
S. R.
,
Van Dyke
R. H.
(
1950
)
The role of the medulla in the differentiation of the otic vesicle.
J. Exp. Zool
113
,
179
199
Ekker
M.
,
Akimenko
M. A.
,
Bremiller
R.
,
Westerfield
M.
(
1992
)
Regional expression of three homeobox transcripts in the inner ear of zebrafish embryos.
Neuron
9
,
27
35
Gallagher
B. C.
,
Henry
J. J.
,
Grainger
R. M.
(
1996
)
Inductive processes leading to inner ear formation during Xenopus development.
Dev. Biol
175
,
95
107
Garcia-Martinez
V.
,
Alvarez
I. S.
,
Schoenwolf
G. C.
(
1993
)
Locations of the ectodermal and nonectodermal subdivisions of the epiblast at stages 3 and 4 of avian gastrulation and neurulation.
J. Exp. Zool
267
,
431
446
Grainger
R. M.
(
1992
)
Embryonic lens induction: shedding light on vertebrate tissue determination.
Trends Genet
8
,
349
355
Groves
A. K.
,
Anderson
D. J.
(
1996
)
Role of environmental signals and transcriptional regulators in neural crest development.
Dev. Genet
18
,
64
72
Groves
A. K.
,
George
K. M.
,
Tissier-Seta
J. P.
,
Engel
J. D.
,
Brunet
J. F.
,
Anderson
D. J.
(
1995
)
Differential regulation of transcription factor gene expression and phenotypic markers in developing sympathetic neurons.
Development
121
,
887
901
Gurdon
J. B.
(
1987
)
Embryonic induction—molecular prospects.
Development
99
,
285
306
Hamburger
V.
,
Hamilton
H. L.
(
1951
)
A series of normal stages in the development of the chick embryo.
J. Morphol
88
,
49
92
Heller
N.
,
Brandli
A. W.
(
1999
)
Xenopus Pax-2/5/8 orthologues: novel insights into Pax gene evolution and identification of Pax-8 as the earliest marker for otic and pronephric cell lineages.
Dev. Genet
24
,
208
219
Herbrand
H.
,
Guthrie
S.
,
Hadrys
T.
,
Hoffmann
S.
,
Arnold
H.-H.
,
Rinkwitz-Brandt
S.
,
Bober
E.
(
1998
)
Two regulatory genes, cNkx5-1 and cPax2 show different responses to local signals during otic placode and vesicle formation in the chick embryo.
Development
125
,
645
654
Jacobson
A. G.
(
1963
)
The determination and positioning of the nose, lens and ear. I. Interactions within the ectoderm, and between the ectoderm and underlying tissues.
J. Exp. Zool
154
,
273
283
Jacobson
A. G.
(
1963
)
The determination and positioning of the nose, lens and ear. II. The role of the endoderm.
J. Exp. Zool
154
,
285
291
Jacobson
A. G.
(
1963
)
The determination and positioning of the nose, lens and ear. III. Effects of reversing the antero-posterior axis of epidermis, neural plate and neural fold.
J. Exp. Zool
154
,
293
303
Jacobson
A. G.
(
1966
)
Inductive processes in embryonic development.
Science
152
,
25
34
Jacobson
A. G.
,
Sater
A. K.
(
1988
)
Features of embryonic induction.
Development
104
,
341
359
Kaan
H. W.
(
1926
)
Experiments on the development of the ear of Amblystoma punctatum.
J. Exp. Zool
46
,
13
61
Meier
S.
(
1978
)
Development of the embryonic chick otic placode. I. Light microscopic analysis.
Anat. Rec
191
,
447
458
Meier
S.
(
1978
)
Development of the embryonic chick otic placode. II. Electron microscopic analysis.
Anat. Rec
191
,
459
477
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
Pfeffer
P. L.
,
Gerster
T.
,
Lun
K.
,
Brand
M.
,
Busslinger
M.
(
1998
).
Characterization of three novel members of the zebrafish Pax2/5/8 family: dependency of Pax5 and Pax8 expression on the Pax2.1 (noi) function.
Development
125
,
3063
3074
Represa
J.
,
Leon
Y.
,
Miner
C.
,
Giraldez
F.
(
1991
)
The int-2 proto-oncogene is responsible for induction of the inner ear.
Nature
353
,
561
563
Sechrist
J.
,
Marcelle
C.
(
1996
)
Cell division and differentiation in avian embryos: techniques for study of early neurogenesis and myogenesis.
Methods Cell Biol
51
,
301
329
Selleck
M. A. J.
(
1996
)
Culture and microsurgical manipulation of the early avian embryo.
Methods Cell Biol
51
,
1
21
Selleck
M. A. J.
,
Bronner-Fraser
M.
(
1995
)
Origins of the avian neural crest: the role of neural plate-epidermal interactions.
Development
121
,
525
538
Stark
M. R.
,
Sechrist
J.
,
Bronner-Fraser
M.
,
Marcelle
C.
(
1997
)
Neural tube/ectoderm interactions are required for trigeminal placode formation.
Development
124
,
4287
4295
Streit
A.
,
Sockanathan
S.
,
Perez
L.
,
Rex
M.
,
Scotting
P. J.
,
Sharpe
P. T.
,
Lovell-Badge
R.
,
Stern
C. D.
(
1997
)
Preventing the loss of competence for neural induction: HGF/SF, L5 and Sox-2.
Development
124
,
1191
1202
Streit
A. C.
,
Stern
C. D.
(
1997
)
Competence for neural induction: HGF/SF, HGF1/MSP and the c-Met receptor.
CIBA Found. Symp
212
,
155
165
Torres
M.
,
Giráldez
F.
(
1998
)
The development of the vertebrate inner ear.
Mech. Dev
71
,
5
21
Torres
M.
,
Gomez-Pardo
E.
,
Gruss
P.
(
1996
)
Pax-2 contributes to inner ear patterning and optic nerve trajectory.
Development
122
,
3381
3391
Vendrell
V.
,
Carnicero
E.
,
Giraldez
F.
,
Alonso
M.T.
,
Schimmang
T.
(
2000
)
Induction of inner ear fate by FGF3.
Development
127
,
2011
2019
Vogel
K. S.
,
Davies
A. M.
(
1993
)
Heterotopic transplantation of presumptive placodal ectoderm changes the fate of sensory neuron precursors.
Development
119
,
263
276
Waddington
C. H.
(
1937
)
The determination of the auditory placode in the chick.
J. Exp. Biol
14
,
232
239
Wolswijk
G.
,
Noble
M.
(
1989
)
Identification of an adult-specific glial progenitor cell.
Development
105
,
387
400
Yntema
C. L.
(
1950
)
An analysis of induction of the ear from foreign ectoderm in the salamander embryo.
J. Exp. Zool
113
,
211
244
Zwilling
E.
(
1940
)
The determination of the otic vesicle in Rana pipiens.
J. Exp. Zool
86
,
333
343
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