Regulation of neurotrophin receptor expression during embryonic and postnatal development

Abstract

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.

Ontogeny of postsynaptic density proteins at glutamatergic synapses

“…The full-length TrkB protein decreased slightly, after an initial increase from E18 to P2, and the truncated protein increased during development. The increase in the full-length TrkB from embryo to early postnatal ages, and the increase in the truncated protein through postnatal development are consistent with published findings (Escandón et al, 1994;Fryer et al, 1996). Only a low level was evident in the P2 PSD II fraction; the only band in this fraction was the full-length form as described for adult brain PSDs (Wu et al, 1996).…”

Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells

“…4e) and that elicited by IGF alone [IGF ϭ 100 Ϯ 4%, IGF ϩ PACAP ϭ 64 Ϯ 5%, (percentage control Ϯ SEM), P Ͻ 0.03] or bFGF alone (bFGF ϭ 100 Ϯ 3%, bFGF ϩ PACAP ϭ 72 Ϯ 2%, P Ͻ 0.007), suggesting that PACAP provides a general signal to induce cell cycle withdrawal. In contrast, the neurotrophins (NT3, BDNF, NGF) survival and differentiation factors expressed in developing cortex (7,8,(23)(24)(25)(26)(27) did not affect DNA synthesis (data not shown), suggesting that PACAP plays a distinct role (note: trophic activity was exhibited by NT3 and NGF in sympathetic, and BDNF in cerebellar granule, cultures).…”

“…Consequently, we characterized PACAP effects on biochemical and morphological markers of differentiation. BDNF and its trkB receptor are widely expressed in developing cortex (25)(26)(27), promoting differentiation and survival (8,23). Initially undetectable at E14, trkB expression in vivo increases progressively with de- velopment (24).…”

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

“…Developing motor neurons express TrkB.FL (Yan et al, 1993;Escandon et al, 1994;McKay et al, 1996), and expression persists into adulthood (Koliatsos et al, 1993;Yan et al, 1997). The expression of TrkB.T1 in motor neurons increases with age (Escandon et al, 1994;Koliatsos et al, 1994;Armanini et al, 1995).…”