Doxakis Epaminondas, Davies Alun M
School of Biosciences, PO Box 911, Cardiff CF10 3US, Wales, UK.
Mol Cell Neurosci. 2005 Aug;29(4):617-27. doi: 10.1016/j.mcn.2005.04.011.
Neurotrophins and members of the GDNF family influence the generation, differentiation and survival of sympathetic neurons during development. Neurotrophin receptor expression and responsiveness has previously been shown to be regulated by all-trans retinoic acid (RA) in embryonic chicken sympathetic neurons. To determine if RA also regulates responsiveness to GDNF family members and expression of their receptors, we studied the effect of treating cultures of these neurons at a stage when they survive in response to GDNF and neurturin. RA caused a dose-dependent decrease in the survival response to both GDNF and neurturin. Transcripts for the ligand-specifying receptors for GDNF and neurturin, GFRalpha-1 and GFRalpha-2, as well as the common signal transducing receptor Ret were all down-regulated by RA treatment in a dose-dependent manner. Transcripts for all three retinoic acid receptors RaRalpha, RaRbeta and RaRgamma as well as the enzymes involved in RA synthesis, Adh-1 and RALDH-2, RALDH-3, were present in both sympathetic targets and neurons. Studies with retinoic acid receptor agonists and antagonists revealed that the effects of RA on receptor expression were mediated mainly by RaRalpha. These findings implicate RA in regulating the actions of members of the GDNF family on developing sympathetic neurons.
神经营养因子和胶质细胞源性神经营养因子（GDNF）家族成员在发育过程中影响交感神经元的生成、分化和存活。先前已证明，在胚胎鸡交感神经元中，全反式视黄酸（RA）可调节神经营养因子受体的表达和反应性。为了确定RA是否也调节对GDNF家族成员的反应性及其受体的表达，我们研究了在这些神经元对GDNF和神经营养素产生反应而存活的阶段，用RA处理这些神经元培养物的效果。RA导致对GDNF和神经营养素的存活反应呈剂量依赖性降低。GDNF和神经营养素的配体特异性受体GFRalpha-1和GFRalpha-2以及共同的信号转导受体Ret的转录本均因RA处理而呈剂量依赖性下调。视黄酸受体RaRalpha、RaRbeta和RaRgamma以及参与RA合成的酶Adh-1和RALDH-2、RALDH-3的转录本在交感神经靶标和神经元中均有表达。对视黄酸受体激动剂和拮抗剂的研究表明，RA对受体表达的影响主要由RaRalpha介导。这些发现表明RA在调节GDNF家族成员对发育中的交感神经元的作用中发挥作用。
