Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression

Abstract

The expression of high affinity neurotrophin receptors (T&A, TrkB, and TrkC) determines the survival response of different populations of neurons to specific members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). However, the mechanism which controls the expression of neurotrophin receptors during neuronal development is largely unknown. Here we show that the treatment of the cultured sympathetic neurons from newborn rat superior cervical ganglia (SCG) with retinoic acid (RA), a derivative of vitamin A, suppressed the expression of trkA mRNA and induced the expression of trkB mRNA. Expression of the functional TrkB receptor was confirmed by the emergence of trophic dependence of these neurons on BDNF in the absence of NGF. Differential regulation of trk mRNAs by RA provides a possible model for the establishment of neurotrophin dependence of peripheral neurons.

Regulation of Glial Cell Line-Derived Neurotrophic Factor Responsiveness in Developing Rat Sympathetic Neurons by Retinoic Acid and Bone Morphogenetic Protein-2

“…For example, RA supports survival and proliferation of neural crest cells (Henion and Weston, 1994). Together with previous studies (Kobayashi et al, 1994(Kobayashi et al, , 1998Holst et al, 1997;Zhang et al, 1998;Wyatt et al, 1999), the present results indicate that RA acts not only during an early stage of neural crest development but also at a later stage of neuronal differentiation by regulating the expression of receptors for neurotrophic factors and hence responsiveness to neurotrophic factors (NT3 and GDNF) that play important roles in the development of these neurons at the embryonic period. For the induction of GDNF responsiveness in cultured SCG neurons from E17 rats, RA markedly induced the expression of ligandspecifying receptor component GFR␣-1 and increased the efficacy of GDNF-triggered Ret tyrosine phosphorylation.…”

“…RA and BMPs are known to possess profound effects in a variety of biological processes, including differentiation of neural crest-derived cells (Kaplan et al, 1993;Henion and Weston, 1994;Kobayashi et al, 1994Kobayashi et al, , 1998Holst et al, 1997;Mehler et al, 1997;Zhang et al, 1998;Wyatt et al, 1999). For example, RA supports survival and proliferation of neural crest cells (Henion and Weston, 1994).…”

“…Previously, it was reported that RA induces the expression of TrkB receptors, which mediates biological action of BDNF (Kaplan et al, 1993;Kobayashi et al, 1994) and suppress the expression of TrkA, which mediates biological action of NGF (Kobayashi et al, 1994;Wyatt et al, 1999). BMP2, however, abolished the effects of RA on the induction of TrkB (M. Kobayashi, unpublished observation) and promoted the effects of RA on the suppression of TrkA (Kobayashi et al, 1998) in cultured SCG neurons, suggesting that the combination of RA and BMP2 specifies the responsiveness of SCG neurons to neurotrophic factors (NT3 and GDNF) that play important roles in the development of these neurons at the embryonic period.…”

Interaction of GRASP, a Protein encoded by a Novel Retinoic Acid-induced Gene, with Members of the Cytohesin Family of Guanine Nucleotide Exchange Factors

“…Retinoid signals induce the expression of a wide array of target genes implicated in mediating the pleiotropic effects of RA on cellular function. These genes encode transcription factors (3)(4)(5)(6)(7)(8)(9), metabolic enzymes (10), growth factor receptors (11), extracellular matrix proteins (12,13), and secreted proteins (14 -16) postulated to convey positional information in the developing embryo.…”

Distribution of BDNF and TrkB isoforms in growing antler tissues of red deer

“…RA is known to modulate differential regulation of the expression of TrkB in neurons and in SH-SY5Y cells (Kobayashi et al, 1994;RuizLeón and Pascual, 2003); thus, it may substantially intensify the effects of BDNF. In antler, RA is synthesized in the perichondrium and keeps the mesenchymal growth zone in a pre-chondrogenic state.…”