The Trk family of tyrosine kinases encodes receptors for nerve growth factor-related neurotrophins. Here we present a developmental expression study of trkC, which encodes a receptor for neurotrophin-3 (NT-3). Like the related genes, trk and trkB, trkC is expressed primarily in neural lineages although the pattern is complex and includes non-neuronal cells. Direct comparison with trk and trkB developmental expression patterns permits the following observations. (1) trkC is expressed in novel neural tissues where other Trk genes are silent. (2) Some tissues appear to coexpress trkB and trkC receptors in the embryo and in the adult. (3) trkC expression can be detected in the gastrulating embryo. These data provide insights into the role of Trk-family receptors and nerve growth factor-related neurotrophins during development and suggest that, in addition to regulating neuronal survival and differentiation, the neurotrophin/Trk receptor system may have broader physiological effects. Finally, interspecific mouse backcrosses have been used to map the location of each of the Trk genes on mouse chromosomes. Alignment with available chromosomal maps identify possible linkage between the Trk genes and known neurological mutations.
Reference
Alonso
S.
, Minty
A.
, Bourlet
Y.
, Buckingham
M.
(1986
) Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates.
J. Molec. Evolution
23
, 11
–22
Altman
J.
, Bayer
S. A.
(1985
) Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements.
J. Comp. Neurol
231
, 1
–6
Aroian
R. V.
, Sternberg
P. W.
(1991
) Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction.
Genetics
128
, 251
–267
Barde
Y.-A.
(1989
) Trophic factors and neuronal survival.
Neuron
2
, 1525
–1534
Berkemeier
L. R.
, Winslow
J. W.
, Kaplan
D. R.
, Nikolics
K.
, Goeddel
D. V.
, Rosenthal
A.
(1991
) Neurotrophin-5: A novel neurotrophic factor that activates trk and trk B.
Neuron
7
, 857
–.Carroll
S. L.
, Silos-Santiago
I.
, Frese
S. E.
, Ruit
K. G.
, Milbrandt
J.
, Snider
W. D.
(1992
) Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero.
Neuron
9
, 779
–788
Chai
C. K.
(1961
) Hereditary spasticity in mice.
J. Hered
52
, 241
–243
Chao
M. V.
(1992
) Neurotrophin receptors: a window into neuronal differentiation.
Neuron
9
, 583
–593
Copeland
N. G.
, Jenkins
N. A.
(1991
) Development and applications of a molecular genetic linkage map of the mouse genome.
Trends Genet
7
, 113
–118
Copeland
N. G.
, Gilbert
D. J.
, Chretien
M.
, Seidah
N. G.
, Jenkins
N. A.
(1992
) Regional localization of three convertases, PC1 (Nec-1), PC2 (Nec-2), and Furin (Fur), on mouse chromosomes.
Genomics
13
, 1356
–1358
Cox
R. D.
, Copeland
N. G.
, Jenkins
N. A.
, Lehrach
H.
(1991
) Interspersed repetitive element polymerase chain reaction product mapping using a mouse interspecific backcross.
Genomics
10
, 375
–384
Ernfors
P.
, Ibáñez
C. F.
, Ebendal
T.
, Olson
L.
, Persson
H.
(1990
) Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: Developmental and topographical expression in the brain.
Proc. Natl. Acad. Sci. USA
87
, 5454
–.Geissler
E. N.
, McFarland
E. C.
, Russel
E. S.
(1981
) Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse: a description of ten new W alleles.
Genetics
97
, 337
–361
Geissler
E. N.
, Ryan
M. A.
, Housman
D. E.
(1988
) The dominant white-spotting (W) locus of the mouse encodes the c- kit proto-oncogene.
Cell
55
, 185
–192
Glass
D. J.
, Nye
S. H.
, Hantzopoulos
P.
, Macchi
M. J.
, Squinto
S. P.
, Goldfarb
M.
, Yancopoulos
G. D.
(1991
) TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor.
Cell
66
, 405
–413
Haefliger
J.-A.
, Bruzzone
R.
, Jenkins
N. A.
, Gilbert
D. J.
, Copeland
N. G.
, Paul
D. L.
(1992
) Four novel members of the connexin family of gap junction proteins.
J. Biol. Chem
267
, 2057
–2064
Hallböök
F.
, Ibáñez
C. F.
, Persson
H.
(1991
) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in xenopus ovary.
Neuron
6
, 845
–.Hempstead
B.
, Kaplan
D. R.
, Martin-Zanca
D.
, Parada
L. F.
, Chao
M. V.
(1991
) High affinity NGF binding requires co-expression of the trk proto-oncogene product and the low affinity NGF receptor.
Nature
350
, 678
–.Hohn
A.
, Leibrock
J.
, Bailey
K.
, Barde
Y.-A.
(1990
) Identification and characterization of a novel member of the nerve growth factor brain-derived neurotrophic factor family.
Nature
344
, 339
–.Holtzman
D. M.
, Li
Y.
, Parada
L. F.
, Kinsman
S.
, Chen
C.-K.
, Valletta
J. S.
, Zhou
J.
, Long
J. B.
, Mobley
W. C.
(1992
) p140 trk mRNA marks NGF responsive forebrain neurons: evidence that trk gene expression is induced by NGF.
Neuron
9
, 465
–478
Ip
N. Y.
, Ibáñez
C. F.
, Nye
S. H.
, McClain
J.
, Jones
P. F.
, Gies
D. R.
, Belluscio
L.
, LeBeau
M. M.
, Espinosa III
R.
, Squinto
S. P.
, Persson
H.
, Yancopoulos
G. D.
(1992
) Mammalian neurotrophin-4: Structure, chromosomal localization, tissue distribution, and receptor specificity.
Proc. Natl. Acad. Sci. USA
89
, 3060
–.Jenkins
N. A.
, Copeland
N. G.
, Taylor
B. A.
, Lee
B. K.
(1982
) Organization, distribution, and stability of endogenous ecotropic murineleukemia virus DNA sequences in chromosomes of Mus musculus.
J. Virol
43
, 26
–36
Jones
K. R.
, Reichardt
L. F.
(1990
) Molecular cloning of the human gene that is a member of the nerve growth factor family.
Proc. Natl. Acad. Sci. USA
87
, 8060
–.Kaisho
Y.
, Yashimura
K.
, Nakahama
K.
(1990
) Cloning and expression of a cDNA encoding a novel human neurotrophic factor.
FEBS Lett
266
, 187
–.Kalcheim
C.
, Carmeli
C.
, Rosenthal
A.
(1992
) Neurotrophin 3 is a mitogen for cultured neural crest cells.
Proc. Natl. Acad. Sci. USA
89
, 1661
–1665
Kaplan
D. R.
, Martin-Zanca
D.
, Parada
L. F.
(1991
) Tyrosine phosphorylation and tyrosine kinase activity of the trk protooncogene product induced by NGF.
Nature
350
, 158
–.Kaplan
D. R.
, Hempstead
B. L.
, Martin-Zanca
D.
, Chao
M. V.
, Parada
L. F.
(1991
) The trk proto-oncogene product: A signal transducing receptor for nerve growth factor.
Science
252
, 554
–.Klein
R.
, Parada
L. F.
, Coulier
F.
, Barbacid
M.
(1989
) Trk B, a novel tyrosine protein kinase receptor expressed during mouse neural development.
EMBO J
8
, 3701
–.Klein
R.
, Martin-Zanca
D.
, Barbacid
M.
, Parada
L. F.
(1990
) Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system.
Development
109
, 845
–.Klein
R.
, Conway
D.
, Parada
L. F.
, Barbacid
M.
(1990
) The trk B tyrosine kinase gene codes for a second neurogenic receptor that lacks the catalytic domain.
Cell
61
, 647
–.Klein
R.
, Jing
S.
, Nanduri
V.
, O'Rourke
E.
, Barbacid
M.
(1991
) The Trk proto-oncogene encodes a receptor for nerve growth factor.
Cell
65
, 189
–.Krieg
P. A.
, Melton
D. A.
(1987
) In vitro RNA synthesis with SP6 RNA polymerase.
Methods Enzymol
155
, 397
–405
Lamballe
F.
, Klein
R.
, Barbacid
M.
(1991
) trk C: a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3.
Cell
66
, 967
–.Le Douarin
N. M.
, Teillet
M. A.
(1973
) The migration of neural crest cells to the wall of the digestive tract in avian embryo.
J. Embryol. Exp. Morph
30
, 31
–48
Leibrock
J.
, Lottspeich
F.
, Hohn
A.
, Hofer
M.
, Hengerer
B.
, Masiakowski
P.
, Thoenen
H.
, Barde
Y.-A.
(1989
) Molecular cloning and expression of brain-derived neurotrophic factor.
Nature
341
, 149
–.Linck
G.
, Stoeckel
M. E.
, Porte
A.
, Petrovic
A.
(1973
) An electron microscope study of the specialized cell contacts and innervation of adipocyte in the brown fat of the european hamster (Cricetus cricetus).
Cytobiologie
7
, 431
–.Loeb
D. M.
, Maragos
J.
, Martin-Zanca
D.
, Chao
M. V.
, Parada
L. F.
, Greene
L. A.
(1991
) The trk proto-oncogene rescues NGF responsiveness in mutant NGF-nonresponsive PC12 cell lines.
Cell
66
, 961
–.Lunsford
R. D.
, Jenkins
N. A.
, Kozak
C. A.
, Liang
L.-F.
, Silan
C. M.
, Copeland
N. G.
, Dean
J.
(1990
) Genomic mapping of murine Zp-2 and Zp-3, two oocyte-specific loci encoding zona pellucida proteins.
Genomics
6
, 184
–187
Maisonpierre
P. C.
, Belluscio
L.
, Squinto
S.
, Ip
N. Y.
, Furth
M. E.
, Lindsay
R. M.
, Yancopoulos
G. D.
(1990
) A neurotrophin-3: A neurotrophic factor related to NGF and BDNF.
Science
247
, 1446
–.Maisonpierre
P. C.
, Belluscio
L.
, Friedman
B.
, Alderson
R. F.
, Wiegand
S. J.
, Furth
M. E.
, Lindsay
R. M.
, Yancopoulos
G. D.
(1990
) NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expressions.
Neuron
5
, 5101
–5109
Martin-Zanca
D.
, Hughes
S. H.
, Barbacid
M.
(1986
) A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences.
Nature
319
, 743
–748
Martin-Zanca
D.
, Oskam
R.
, Mitra
G.
, Copeland
T.
, Barbacid
M.
(1989
) Molecular and biochemical characterization of the human trk proto-oncogene.
Mol. Cell. Biol
9
, 24
–.Martin-Zanca
D.
, Barbacid
M.
, Parada
L. F.
(1990
) Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development.
Genes Dev
4
, 683
–.Miozzo
M.
, Pierotti
M. A.
, Sozzi
G.
, Radie
P.
, Bongarzone
I.
, Spurr
L.
Tessarollo and others475Developmental expression of the trkC receptor tyrosine kinaseN. K. and Della Porta, G
(1990
) Human TRK proto-oncogene maps to chromosome 1q32-q41.
Oncogene
5
, 1411
–1414
Morris
C. M.
, Hao
Q. L.
, Heisterkamp
N.
, Fitzgerald
P. H.
, Groffen
J.
(1991
) Localization of the TRK proto-oncogene to human chromosome bands 1q23-1q24.
Oncogene
6
, 1093
–1095
Mucenski
M. L.
, Taylor
B. A.
, Copeland
N. G.
, Jenkins
N. A.
(1988
) Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors.
Oncogene Res
2
, 219
–233
Mullen
R. J.
(1977
) Site of pcd gene action and Purkinje cell mosaicism in cerebella of chimeric mice.
Nature
270
, 245
–247
Mullen
R. J.
, Eicher
E. M.
, Sidman
R. L.
(1976
) Purkinje cell degeneration, a new neurological mutation in the mouse.
Proc. Natl. Acad. Sci. USA
73
, 208
–212
Neumann
P. E.
, Collins
R. L.
(1991
) Genetic dissection of susceptibility to audiogenic seizures in inbred mice.
Proc. Natl. Acad. Sci. USA
88
, 5408
–5412
O'Gorman
S.
(1985
) Degeneration of thalamic nuclei in ‘Purkinje cell degeneration' mutant mice. II. Cytology of neuron loss.
J. Comp. Neurol
234
, 298
–316
Oppenheim
R. W.
, Qin-Wei
Y.
, Prevette
D.
, Yan
Q.
(1992
) Brain-derived nerotrophic factor rescues developing avian motoneurons from cell death.
Nature
360
, 755
–757
Otten
U.
, Ehrhard
P.
, Peck
R.
(1989
) Nerve growth factor induces growth and differentiation of human B lymphocytes.
Proc. Natl. Acad. Sci. USA
86
, 10059
–10063
Parada
L. F.
, Tsoulfas
P.
, Tessarollo
L.
, Blair
J.
, Reid
S.
, Soppet
D.
(1992
) The Trk family of tyrosine kinases: receptors for NGF-related neurotrophins. In CSH Series. Cold Spring Harbor Symp.
Quant. Biol
57
, 43
–51
Parvinen
M.
, Pelto-Huikko
M.
, Soder
O.
, Schultz
R.
, Kaipia
A.
, Mali
P.
, Toppari
J.
, Hakovirta
H.
, Lönnerberg
P.
, Ritzen
E.M.
, Ebendal
T.
, Olson
L.
, Hökfelt
T.
, Persson
H.
(1992
) Expression of-Nerve Growth Factor and its receptor in rat seminiferous epithelium: specific function at the onset of meiosis.
J. Cell Biol
117
, 629
–641
Pirvola
U.
, Ylikoski
J.
, Palgi
J.
, Lehtonen
E.
, Arumäe
U.
, Saarma
M.
(1992
) Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia.
Proc. Natl. Acad. Sci. USA
89
, 9915
–9919
Rosenthal
A.
, Goeddel
D. V.
, Nyugen
T.
, Lewis
M.
, Shih
A.
, Laramee
G. R.
, Nikolics
K.
, Winslow
J. W.
(1990
) Primary structure and biological activity of a novel human neurotrophic factor.
Neuron
4
, 767
–773
Sendtner
M.
, Schmalbruch
H.
, Stockli
K. A.
, Carrol
P.
, Kreutzberg
G. W.
, Thoenen
H.
(1992
) Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy.
Nature
358
, 502
–504
Sendtner
M.
, Holtmann
B.
, Kolbeck
R.
, Thoenen
H.
, Barde
Y.-A.
(1992
) Brain-derived neurotrophin factor prevents the death of motoneurons in newborn rats after nerve section.
Nature
360
, 757
–759
Soppet
D.
, Escandon
E.
, Maragos
J.
, Middlemas
D. S.
, Reid
S. W.
, Blair
J.
, Burton
L. E.
, Stanton
B. R.
, Kaplan
D. R.
, Hunter
T.
, Nikolics
K.
, Parada
L. F.
(1991
) The neurotrophic factor and neurotrophin-3 are ligands for the trk B tyrosine kinase receptor.
Cell
65
, 895
–.Squinto
S. P.
, Stitt
T. N.
, Aldrich
T. H.
, Davis
S.
, Bianco
S. M.
, Radziejewski
C.
, Glass
D. J.
, Masiakowski
P.
, Furth
M. E.
, Valenzuela
D. M.
, DiStefano
P. S.
, Yancopoulos
G. D.
(1991
) Trk B encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but nerve growth factor.
Cell
54
, 885
–.Tessarollo
L.
, Nagarajan
L.
, Parada
L. F.
(1992
) C- ros: the vertebrate homolog of the sevenless tyrosine kinase receptor is tightly regulated during organogenesis in mouse embryonic development.
Development
115
, 11
–.Van Heyningen
V.
, Bobrow
M.
, Bodmer
W. F.
, Gardiner
S. E.
, Povey
S.
, Hopkinson
D. A.
(1975
) Chromosome assignment of some human enzyme loci: mitochondrial malate dehydrogenase to 7, mannose phosphate isomerase and pyruvate kinase to 15 and probably, esterase D to 13.
Ann. Hum. Genet
38
, 295
–303
Van Snick
J.
, Goethals
A.
, Renauld
J.-C.
, Van Roost
E.
, Uyttenhove
C.
, Rubira
M. R.
, Moritz
R. L.
, Simpson
R. J.
(1989
) Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40).
J. Exp. Med
169
, 363
–368
White
W. F.
(1985
) The glycine receptor in the mutant mouse spastic (spa): strychnine binding characteristics and pharmacology.
Brain Res
329
, 1
–6
White
W. F.
, Heller
A. H.
(1982
) Glycine receptor alteration in the mutant mouse spastic.
Nature
298
, 655
–657
Wilson
D. E.
, Woodard
D.
, Sandler
A.
, Erikson
J.
, Gurney
A.
(1986
) The gene for uridine monophosphatase-2 is on mouse chromosome 11.
Am. J. Hum. Genet
39
, 173
–.Yan
Q.
, Elliott
J.
, Snider
W. D.
(1992
) Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death.
Nature
360
, 753
–755
This content is only available via PDF.
© 1993 by Company of Biologists
1993
-HUBSwebinar.jpg?versionId=4486)
(update)-InPreprints.png?versionId=4486)
