Regulation of neurotrophin receptor expression during embryonic and postnatal development.
Members of the NGF family of proteins act as neurotrophic agents for defined populations of peripheral and central neurons during embryonic and postnatal development. We have studied the presence of receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4/5 (NT-3, NT-4/5) by cross-linking radioiodinated neurotrophins to specific cell surface receptors. We have identified neurotrophin receptors representing full-length TrkB and TrkC and their truncated forms (lacking a functional cytoplasmic kinase domain) in neuronal as well as in non-neuronal tissues. During chicken embryonic and early postnatal brain development, expression of full-length TrkB and TrkC proteins preceded the onset of the truncated forms of these receptors. A similar pattern was also observed in mouse embryonic and early postnatal brain. The relative levels of neurotrophin receptors in the basal forebrain and in the hippocampus did not change significantly with age in mice. High levels of receptors for the three neurotrophins were detected in the nigrostriatal system. Full-length TrkB and TrkC receptors were found in chicken and rat embryonic ventral spinal cord, as well as on purified motoneurons. Again, truncated TrkB appeared significantly later than the full-length form on spinal motoneurons. In chicken embryonic retina and optic tectum we detected full-length TrkB and TrkC; however, the optic tectum also expressed large amounts of the truncated form of TrkB. TrkC but not TrkB was detected in chicken embryonic skeletal muscle, suggesting that NT-3 may have a novel function in this tissue. The presence of neurotrophin receptors in a wide variety of embryonic and postnatal tissues underlines the significant role of BDNF, NT-3, and NT-4/5 in embryonic and postnatal development. The regulation of the ratio of full-length versus truncated neurotrophin receptors may play an important role in the development, maturation, and maintenance of various neuronal networks.
Escandón
E
E
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080-4990.
Soppet
D
D
Rosenthal
A
A
Mendoza-Ramírez
J L
JL
Szönyi
E
E
Burton
L E
LE
Henderson
C E
CE
Parada
L F
LF
Nikolics
K
K
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor; D002462:Cell Membrane / Q000378:metabolism; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation; D005865:Gestational Age; D007106:Immune Sera; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020933:Neurotrophin 3; D009928:Organ Specificity; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D007106:Immune Sera; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D010455:Peptides; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC; C073922:neurotrophin 4