The zebrafish detour (dtr) mutation generates a novel neuronal phenotype. In dtr mutants, most cranial motor neurons, especially the branchiomotor, are missing. However, spinal motor neurons are generated normally. The loss of cranial motor neurons is not due to aberrant hindbrain patterning, failure of neurogenesis, increased cell death or absence of hh expression. Furthermore, activation of the Hh pathway, which normally induces branchiomotor neurons, fails to induce motor neurons in the dtr hindbrain. Despite this, not all Hh-mediated regulation of hindbrain development is abolished since the regulation of a neural gene by Hh is intact in the dtr hindbrain. Finally, dtr can function cell autonomously to induce branchiomotor neurons. These results suggest that detour encodes a component of the Hh signaling pathway that is essential for the induction of motor neurons in the hindbrain but not in the spinal cord and that dtr function is required for the induction of only a subset of Hh-mediated events in the hindbrain.

Reference

Allende
M. L.
,
Weinberg
E. S.
(
1994
)
The expression pattern of two zebrafish achaete-scute homolog (ash) genes is altered in the embryonic brain of the cyclops mutant.
Dev. Biol
166
,
509
530
Appel
B.
,
Korzh
V.
,
Glasgow
E.
,
Thor
S.
,
Edlund
T.
,
Dawid
I. B.
,
Eisen
J. S.
(
1995
)
Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish.
Development
121
,
4117
4125
Bang
A. G.
,
Papalopulu
N.
,
Kintner
C.
,
Goulding
M. D.
(
1997
)
Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm.
Development
124
,
2075
2085
Beattie
C. E.
,
Hatta
K.
,
Halpern
M. E.
,
Liu
H.
,
Eisen
J. S.
,
Kimmel
C. B.
(
1997
)
Temporal separation in the specification of primary and secondary motoneurons in zebrafish.
Dev. Biol
187
,
171
182
Blader
P.
,
Fischer
N.
,
Gradwohl
G.
,
Guillemont
F.
,
Strahle
U.
(
1997
)
The activity of neurogenin1 is controlled by local cues in the zebrafish embryo.
Development
124
,
4557
4569
Brand
M.
,
Heisenberg
C. P.
,
Warga
R. M.
,
Pelegri
F.
,
Karlstrom
R. O.
,
Beuchle
D.
,
Picker
A.
,
Jiang
Y. J.
,
Furutani-Seiki
M.
,
van Eeden
F. J.
,
Granato
M.
,
Haffter
P.
,
Hammerschmidt
M.
,
Kane
D. A.
,
Kelsh
R. N.
,
Mullins
M. C.
,
Odenthal
J.
,
Nusslein-Volhard
C.
(
1996
)
Mutations affecting development of the midline and general body shape during zebrafish embryogenesis.
Development
123
,
129
142
Burrill
J. D.
,
Easter
S. S.
Jr.
(
1994
)
Development of the retinofugal projections in the embryonic and larval zebrafish (Brachydanio rerio).
J. Comp. Neurol
346
,
583
600
Chandrasekhar
A.
,
Moens
C. B.
,
Warren
J. T.
Jr.
,
Kimmel
C. B.
,
Kuwada
J. Y.
(
1997
)
Development of branchiomotor neurons in zebrafish.
Development
124
,
2633
2644
Chandrasekhar
A.
,
Warren
J. T.
,
Takahashi
K.
,
Schauerte
H. E.
,
van Eeden
F. J. M.
,
Haffter
P.
,
Kuwada
J. Y.
(
1998
)
Role of sonic hedgehog in branchiomotor neuron induction in zebrafish.
Mech. Dev
76
,
101
115
Chitnis
A. B.
,
Kuwada
J. Y.
(
1990
)
Axonogenesis in the brain of zebrafish embryos.
J. Neurosci
10
,
1892
1905
Eisen
J. S.
,
Myers
P. Z.
,
Westerfield
M.
(
1986
)
Pathway selection by growth cones of identified motoneurones in live zebrafish embryos.
Nature
320
,
269
271
Ekker
S. C.
,
Ungar
A. R.
,
Greenstein
P.
,
von Kessler
D. P.
,
Porter
J. A.
,
Moon
R. T.
,
Beachy
P. A.
(
1995
)
Patterning activities of vertebrate hedgehog proteins in the developing eye and brain.
Curr. Biol
5
,
944
955
Ensini
M.
,
Tsuchida
T. N.
,
Belting
H. G.
,
Jessell
T. M.
(
1998
)
The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm.
Development
125
,
969
982
Ericson
J.
,
Morton
S.
,
Kawakami
A.
,
Roelink
H.
,
Jessell
T. M.
(
1996
)
Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity.
Cell
87
,
661
673
Ericson
J.
,
Muhr
J.
,
Placzek
M.
,
Lints
T.
,
Jessell
T. M.
,
Edlund
T.
(
1995
)
Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube.
Cell
81
,
747
756
Ericson
J.
,
Rashbass
P.
,
Schedl
A.
,
Brenner-Morton
S.
,
Kawakami
A.
,
van Heyningen
V.
,
Jessell
T. M.
,
Briscoe
J.
(
1997
)
Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.
Cell
90
,
169
180
Gilland
E.
,
Baker
R.
(
1993
)
Conservation of neuroepithelial and mesodermal segments in the embryonic vertebrate head.
Acta Anat
148
,
110
123
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
Haffter
P.
,
Granato
M.
,
Brand
M.
,
Mullins
M. C.
,
Hammerschmidt
M.
,
Kane
D. A.
,
Odenthal
J.
,
van Eeden
F. J.
,
Jiang
Y. J.
,
Heisenberg
C.-P.
,
Kelsh
R. N.
,
Furutani-Seiki
M.
,
Vogelsang
E.
,
Beuchle
D.
,
Schach
U.
,
Fabian
C.
,
Nusslein-Volhard
C.
(
1996
)
The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio.
Development
123
,
1
36
Hammerschmidt
M.
,
Bitgood
M. J.
,
McMahon
A. P.
(
1996
)
Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo.
Genes Dev
10
,
647
658
Hatta
K.
(
1992
)
Role of the floor plate in axonal patterning in the zebrafish CNS.
Neuron
9
,
629
642
Henion
P. D.
,
Raible
D. W.
,
Beattie
C. E.
,
Stoesser
K. L.
,
Weston
J. A.
,
Eisen
J. S.
(
1996
)
Screen for mutations affecting development of zebrafish neural crest.
Dev. Genet
18
,
11
17
Inoue
A.
,
Takahashi
M.
,
Hatta
K.
,
Hotta
Y.
,
Okamoto
H.
(
1994
)
Developmental regulation of islet-1 mRNA expression during neuronal differentiation in embryonic zebrafish.
Dev. Dyn
199
,
1
11
Kanki
J. P.
,
Chang
S.
,
Kuwada
J. Y.
(
1994
)
The molecular cloning and characterization of potential chick DM-GRASP homologs in zebrafish and mouse.
J. Neurobiol
25
,
831
845
Karlstrom
R. O.
,
Trowe
T.
,
Klostermann
S.
,
Baier
H.
,
Brand
M.
,
Crawford
A. D.
,
Grunewald
B.
,
Haffter
P.
,
Hoffmann
H.
,
Meyer
S. U.
,
Muller
B. K.
,
Richter
S.
,
van-Eeden
F. J.
,
Nusslein-Volhard
C.
,
Bonhoeffer
F.
(
1996
)
Zebrafish mutations affecting retinotectal axon pathfinding.
Development
123
,
427
438
Kim
C. H.
,
Ueshima
E.
,
Muraoka
O.
,
Tanaka
H.
,
Yeo
S. Y.
,
Huh
T. L.
,
Miki
N.
(
1996
)
Zebrafish elav /HuC homologue as a very early neuronal marker.
Neurosci. Lett
216
,
109
112
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
Krauss
S.
,
Concordet
J. P.
,
Ingham
P. W.
(
1993
)
A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos.
Cell
75
,
1431
1444
Lauderdale
J. D.
,
Davis
N. M.
,
Kuwada
J. Y.
(
1997
)
Axon tracts correlate with netrin-1a expression in the zebrafish embryo.
Mol. Cell. Neurosci
9
,
293
313
Lauderdale
J. D.
,
Pasquali
S. K.
,
Fazel
R.
,
van Eeden
F. J. M.
,
Schauerte
H. E.
,
Haffter
P.
,
Kuwada
J. Y.
(
1998
)
Regulation of netrin-1a expression by hedgehog proteins.
Mol. Cell. Neurosci
11
,
194
205
Liem
K. F.
Jr
,
Tremml
G.
,
Jessell
T. M.
(
1997
)
A role for the roof plate and its resident TGFb-related proteins in neuronal patterning in the dorsal spinal cord.
Cell
91
,
127
138
Lumsden
A.
,
Keynes
R.
(
1989
)
Segmental patterns of neuronal development in the chick hindbrain.
Nature
337
,
424
428
Lumsden
A.
,
Krumlauf
R.
(
1996
)
Patterning the vertebrate neuraxis.
Science
274
,
1109
1115
Moens
C. B.
,
Cordes
S. P.
,
Giorgianni
M. W.
,
Barsh
G. S.
,
Kimmel
C. B.
(
1998
)
Equivalence in the genetic control of hindbrain segmentation in fish and mouse.
Development
125
,
381
391
Muhr
J.
,
Jessell
T. M.
,
Edlund
T.
(
1997
)
Assignment of early caudal identity to neural plate cells by a signal from caudal paraxial mesoderm.
Neuron
19
,
487
502
Myers
P. Z.
,
Eisen
J. S.
,
Westerfield
M.
(
1986
)
Development and axonal outgrowth of identified motoneurons in the zebrafish.
J. Neurosci
6
,
2278
2289
Osumi
N.
,
Hirota
A.
,
Ohuchi
H.
,
Nakafuku
M.
,
Iimura
T.
,
Kuratani
S.
,
Fujiwara
M.
,
Noji
S.
,
Eto
K.
(
1997
)
Pax-6 is involved in the specification of hindbrain motor neuron subtype.
Development
124
,
2961
2972
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
Piperno
G.
,
Fuller
M. T.
(
1985
)
Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms.
J. Cell Biol
101
,
2085
2094
Roelink
H.
,
Porter
J. A.
,
Chiang
C.
,
Tanabe
Y.
,
Chang
D. T.
,
Beachy
P. A.
,
Jessell
T. M.
(
1995
)
Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis.
Cell
81
,
445
455
Schauerte
H. E.
,
van Eeden
F. J. M.
,
Fricke
C.
,
Odenthal
J.
,
Strahle
U.
,
Haffter
P.
(
1998
)
Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish.
Development
125
,
2983
2993
Tanabe
Y.
,
Jessell
T. M.
(
1996
)
Diversity and pattern in the developing spinal cord.
Science
274
,
1115
1123
Trevarrow
B.
,
Marks
D. L.
,
Kimmel
C. B.
(
1990
)
Organization of hindbrain segments in the zebrafish embryo.
Neuron
4
,
669
679
Ungar
A. R.
,
Moon
R. T.
(
1996
)
Inhibition of protein kinase A phenocopies ectopic expression of hedgehog in the CNS of wild-type and cyclops mutant embryos.
Dev. Biol
178
,
186
191
Warren
J. T.
,
Chandrasekhar
A.
,
Kanki
J. P.
,
Rangarajan
R.
,
Furley
A.
,
Kuwada
J. Y.
(
1999
)
Molecular cloning and developmental expression of zebrafish glycoprotein TAG-1.
Mech. Dev
80
,
197
201
Woo
K.
,
Fraser
S. E.
(
1997
)
Specification of the zebrafish nervous system by nonaxial signals.
Science
277
,
254
257
Xu
Q.
,
Alldus
G.
,
Holder
N.
,
Wilkinson
D. G.
(
1995
)
Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain.
Development
121
,
4005
4016
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