Developmentally regulated expression of the nerve growth factor receptor gene in the periphery and brain.

Abstract

Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2-to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.Formation of the nervous system is dependent on a complex interaction of genetic and epigenetic factors and signals. Nerve growth factor (NGF) is required for neuronal survival in vivo and elicits diverse responses, including neurite elongation, neurotransmitter enzyme induction, and target-specific innervation in responsive neurons. The many actions of NGF on responsive neurons are initiated by interaction with a specific cell membrane-bound receptor. The NGF-receptor complex is internalized and transported from nerve terminals to the neuronal cell body, where critical cellular processes are mediated (1). Kinetic analyses have indicated that there are high-and low-affinity forms of the receptor molecule (2-4). Finally, 125I-labeled NGF binding in conjunction with cross-linking agents has allowed characterization of the ligand-receptor complex (5-9).We The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Apoptosis in human skin development: Morphogenesis, periderm, and stem cells

“…It follows that this structure must be protected from cell death, especially during the degenerative changes that occur during catagen phase of the hair cycle. Consistent with this conclusion, another factor associated with cell survival, the nerve growth factor receptor (Buck et al, 1987;Sirota et al, 19911, co-distributes with Bcl-2 expression in the dermal papilla of the fetal hair follicle and may participate in the preservation of this structure. The significance of this finding is unknown but may relate to the continuous expression of bcl-2 in growth factor-dependent cells (Allsopp et al, 1993) and may indicate a role of bcl-2 in regulation of the survival of mesenchymal cells and dividing keratinocytes.…”

“…5E,F). This pattern of Bcl-2 in the dermal papilla is reminiscent of that of the pattern of nerve growth factor receptor (NGFR), associated with cell survival in other cell types (Buck et al, 1987;Sirota et al, 1991). NGFR co-localizes with Bcl-2 expression in the dermal papilla, but is not present in the hair matrix cells (Fig.…”

Nerve growth factor corrects developmental impairments of basal forebrain cholinergic neurons in the trisomy 16 mouse.

“…Ts16 mouse fetuses were obtained by breeding normal C57BL/6J females with males that are doubly heterozygous for Robertsonian translocation, Rb(16. 17)7BNR/ RB(9.16)9RMA, as described by Gearhart et al (24) 16.…”

“…In the central nervous system, cholinergic neurons of the BF have been demonstrated to express NGF receptors (16), retrogradely transport NGF from their terminals to the perikarya (17), and respond to NGF in both in vivo and in vitro studies (18)(19)(20). As the BF cholinergic neuronal atrophy and degeneration induced by axonal transsection can be reversed by exogenously administered NGF, this suggests that NGF may be an essential trophic factor for the metabolic maintenance and survival of BF cholinergic neurons (21,22).…”

Pancreatic acinar AR42J cells express functional nerve growth factor receptors

“…The probes used in this study were: a 2·8-kb BamHIEcoRI fragment from the p5b plasmid corresponding to rat p75 NGFR (Buck et al 1987), a 350-base pair (bp) insert and a 464-bp XbaI-SacI fragment from the plasmid pDM97 corresponding to the kinase and the extracellular domain of rat Trk-A, respectively, as described previously (Scharfmann et al 1993), a 2·2-kb insert corresponding to rat c-fos (Curran & Morgan 1985), a 1·9-kb c-jun cDNA (Lamph et al 1988), a 3-kb NGFI-A cDNA (Milbrandt 1987), and a 1·1-kb BamH1 fragment derived from a rat vgf genomic clone (Levi et al 1985).…”