The tyrosine kinase receptor trkB is thought to mediate the biological actions of brain-derived neurotrophic factor. This receptor is expressed by a large variety of neurons during development. Truncated trkB molecules lacking the tyrosine kinase domain have also been described, but their functions remain elusive. In order to gain insight into their role, we studied the pattern of expression and properties of these truncated receptors in the chick embryo. mRNA coding for truncated trkB was detected already early during neurogenesis and in situ hybridisation experiments indicated that the expression was in non-neuronal cells, as previously observed in the brain of adult rodents. Ependymal and leptomeningeal cells expressing high levels of truncated trkB were found to completely surround the developing brain and the spinal cord throughout development. In the otic vesicle, mesenchymal cells expressing truncated trkB surround cells producing brain-derived neurotrophic factor, as well as neurons expressing trkB with its tyrosine kinase domain. Non-neuronal cells were found not to express trkB mRNA coding for the tyrosine kinase domain. Studies with radioiodinated brain-derived neurotrophic factor performed on frozen sections of the chick embryo revealed that non-neuronal cells expressing truncated trkB bind brain-derived neurotrophic factor with high affinity and selectivity. In addition, experiments with dissociated leptomeningeal cells revealed that binding is rapidly followed by selective internalisation of the ligand. These results suggest that truncated trkB molecules form an efficient and selective barrier preventing the diffusion of brain-derived neurotrophic factor and eliminating it by internalisation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reference

Allendoerfer
K. L.
,
Cabelli
R. J.
,
Escandon
E.
,
Kaplan
D. R.
,
Nikolics
K.
,
Shatz
C.
(
1994
)
Regulation of neurotrophin receptors during the maturation of the mammalian visual system.
J. Neurosci
14
,
1795
1811
Barbacid
M.
(
1994
)
The trk family of neurotrophin receptor.
J. Neurobiol
25
,
1386
1403
Beck
K. D.
,
Lamballe
F.
,
Klein
R.
,
Barbacid
M.
,
Schauwecker
P. E.
,
McNeill
T. H.
,
Hefti
F.
,
Day
J. R.
(
1993
)
Induction of noncatalytic TrkB neurotrophin receptors during axonal sprouting in the adult hippocampus.
J. Neurosci
13
,
4001
4014
Biffo
S.
,
Marti
E.
,
Fasolo
A.
(
1992
)
NGF receptor, carnosine and TH m-RNA ontogeny in the olfactory bulb: evidence for different developmental patterns and cellular localisation.
J. Chem. Neuroan
5
,
51
62
Chomczynski
P.
,
Sacchi
N.
(
1987
)
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal. Biochem
162
,
156
159
Davies
A. M.
,
Thoenen
H.
,
Barde
Y.-A.
(
1986
)
The response of chick sensory neurons to brain-derived neurotrophic factor.
J. Neurosci
6
,
1897
1904
Davies
A. M.
(
1994
)
The role of neurotrophins in the developing nervous system.
J. Neurobiol
25
,
1335
1348
Dechant
G.
,
Biffo
S.
,
Okazawa
H.
,
Kolbeck
R.
,
Pottgiesser
J.
,
Barde
Y. A.
(
1993
)
Expression and binding characteristics of the BDNF receptor chick trkB.
Development
119
,
545
558
Ernfors
P.
,
Lee
K.
,
Jaenisch
R.
(
1994
)
Mice lacking brain-derived neurotrophic factor develop with sensory deficits.
Nature
368
,
147
150
Escandon
E.
,
Soppet
D.
,
Rosenthal
A.
,
Mendoza-Ramirez
J. L.
,
Szonyi
E.
,
Henderson
C. E.
,
Parada
L. F.
,
Nikolics
K.
(
1994
)
Regulation of neurotrophin receptor expression during embryonic and postnatal development.
J. Neurosci
14
,
2054
2068
Frisen
J.
,
Verge
V. M.
,
Fried
K.
,
Risling
M.
,
Persson
H.
,
Trotter
J.
,
Lindholm
D.
(
1993
)
Characterization of glial trkB receptors: differential response to injury in the central and peripheral nervous systems.
Proc. Natl. Acad. Sci. USA
90
,
4971
4975
Funakoshi
H.
,
Frisen
J.
,
Barbany
G.
,
Timmusk
T.
,
Zachrisson
O.
,
Verge
V. M.
(
1993
)
Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve.
J. Cell Biol
123
,
455
465
Garner
A.
,
Large
T.
(
1994
)
Isoforms of the avian trkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival.
Neuron
13
,
457
472
Gurdon
J. B.
,
Harger
P.
,
Mitchell
A.
,
Lemaire
P.
(
1994
)
Activin signalling and response to a morphogen gradient.
Nature
371
,
487
492
Hallböök
F.
,
Ayer-Lelievre
C.
,
Ebendal
T.
,
Persson
H.
(
1990
)
Expression of nerve growth factor receptor mRNA during early development of the chicken embryo: emphasis on cranial ganglia.
Development
108
,
693
704
Hamburger
V.
,
Hamilton
L.
(
1951
)
A series of normal stages in the development of the chick embryo.
J. Morph
88
,
49
92
Herzog
K.
,
Bailey
K.
,
Barde
Y.
(
1994
)
Expression of the BDNF gene in the developing visual system of the chick.
Development
120
,
1643
1649
Jing
S.
,
Tapley
P.
,
Barbacid
M.
(
1992
)
Nerve growth factor mediates signal transduction through trk homodimer receptors.
Neuron
9
,
1067
1079
Jones
K. R.
,
Farinas
I.
,
Backus
C.
,
Reichardt
L. F.
(
1994
)
Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development.
Cell
76
,
989
999
Klein
R.
,
Conway
D.
,
Parada
L.F.
,
Barbacid
M.
(
1990
)
The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain.
Cell
61
,
647
656
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
850
Laemmli
U.
(
1970
)
Cleavage of structural protein during the assembly of bacteriophage T4.
Nature
227
,
680
685
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 the mouse development.
Genes Dev
4
,
683
694
Rodríguez-Tebar
A.
,
Barde
Y.-A.
(
1988
)
Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo.
J. Neurosci
8
,
3337
3342
Rodríguez-Tebar
A.
,
Dechant
G.
,
Barde
Y.A.
(
1990
)
Binding of brain-derived neurotrophic factor to the nerve growth factor receptor.
Neuron
4
,
487
492
Schecterson
L. C.
,
Bothwell
M.
(
1992
)
Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons.
Neuron
9
,
449
463
Sieber-Blum
M.
(
1991
)
Role of the neurotrophic factors BDNF and NGF in the commitment of pluripotent neural crest cells.
Neuron
6
,
949
955
Snider
W. D.
(
1994
)
Functions of the neurotrophins during nervous system development: what the knockouts are teaching us.
[Review]. Cell
77
,
627
638
Soppet
D.
,
Escandon
E.
,
Maragos
J.
,
Middlemas
D. S.
,
Reid
S.W.
,
Blair
J.
,
Burton
L.
,
Stanton
B. R.
,
Kaplan
D. R.
,
Hunter
T.
,
Nicolics
K.
,
Parada
L. F.
(
1991
)
The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the tyrosine kinase trkB receptor.
Cell
65
,
1
20
Tessarollo
L.
,
Tsoulfas
P.
,
Martin-Zanca
D.
,
Gilbert
D.
,
Jenkins
N.
,
Copeland
N.
,
Parada
L.F.
(
1993
)
TrkC a receptor for neurotrophin-3 is widely expressed in the developing nervous system and in non-neuronal tissues.
Development
118
,
463
475
Tsoulfas
P.
,
Soppet
D.
,
Escandon
E.
,
Tessarollo
L.
,
Mendoza-Ramirez
J.-L.
,
Rosenthal
A.
,
Nikolics
K.
,
Parada
L. F.
(
1993
)
The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 In PC12 cells.
Neuron
10
,
975
990
Valenzuela
D. M.
,
Maisonpierre
P. C.
,
Glass
D. J.
,
Rojas
E.
,
Nunez
L.
,
Kong
Y.
,
Stitt
T.N.
,
Ip
N. Y.
,
Yancopoulos
G. D.
(
1993
)
Alternative forms of rat TrkC with different functional capabilities.
Neuron
10
,
963
974
Vinh
N. Q.
,
Erdmann
K. S.
,
Heumann
R.
(
1994
)
Cloning and sequence analysis of a cDNA encoding a novel truncated form of the chicken TrkB receptor.
Gene
149
,
383
384
Wilkinson
D. G.
,
Bailes
J. A.
,
Champion
J. E.
,
McMahon
A. P.
(
1987
)
A molecular analysis of mouse development from 8 to 10 days post coitum detects changes only in embryonic globin expression.
Development
99
,
493
500
Wright
E. M.
,
Vogel
K. S.
,
Davies
A.
(
1992
)
Neurotrophic factors promote the maturation of developing sensory neurons before they become dependent on these factors for survival.
Neuron
9
,
139
150
Yan
Q.
,
Matheson
C.
,
Sun
J.
,
Radeke
M. J.
,
Feinstein
S. C.
,
Miller
J. A.
(
1994
)
Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression.
Exp. Neurol
127
,
23
36
This content is only available via PDF.