Garcès A, Livet J, Grillet N, Henderson C E, Delapeyrière O
INSERM U.382, Developmental Biology Institute of Marseille, CNRS-INSERM-Université de la Méditerranée, AP de Marseille, Campus de Luminy, Case 907, 13288 Marseille Cedex 09, France.
Dev Dyn. 2001 Mar;220(3):189-97. doi: 10.1002/1097-0177(20010301)220:3<189::AID-DVDY1106>3.0.CO;2-I.
Glial cell-line derived neurotrophic factor (GDNF) and its relative neurturin (NTN) are both potent trophic factors for motoneurons. They exert their biological effects by activating the RET tyrosine kinase in the presence of a GPI-linked coreceptor, either GFR alpha 1 (considered to be the favored coreceptor for GDNF) or GFR alpha 2 (the preferred NTN coreceptor). By whole-mount in situ hybridization on embryonic rat spinal cord, we demonstrate that, whereas Ret is expressed by nearly all motoneurons, Gfra1 and Gfra2 exhibit complementary and sometimes overlapping patterns of expression. In the brachial and sacral regions, the majority of motoneurons express Gfra1 but only a minority express Gfra2. Accordingly, most motoneurons purified from each region are kept alive in culture by GDNF. However, brachial motoneurons respond poorly to NTN, whereas NTN maintains as many sacral motoneurons as does GDNF. Thus, spinal motoneurons are highly heterogeneous in their expression of receptors for neurotrophic factors of the GDNF family, but their differing responses to NTN are not correlated with expression levels of Gfra1 or Gfra2.
胶质细胞源性神经营养因子（GDNF）及其相关因子神经营养素（NTN）都是对运动神经元有强大作用的营养因子。它们在糖基磷脂酰肌醇（GPI）连接的共受体（GFRα1，被认为是GDNF的优势共受体；或GFRα2，NTN的首选共受体）存在的情况下，通过激活RET酪氨酸激酶发挥生物学效应。通过对胚胎大鼠脊髓进行全胚胎原位杂交，我们证明，虽然Ret几乎在所有运动神经元中都有表达，但Gfra1和Gfra2呈现互补且有时重叠的表达模式。在臂部和骶部区域，大多数运动神经元表达Gfra1，但只有少数表达Gfra2。因此，从每个区域纯化的大多数运动神经元在培养中通过GDNF得以存活。然而，臂部运动神经元对NTN反应不佳，而NTN维持存活的骶部运动神经元数量与GDNF相当。因此，脊髓运动神经元对GDNF家族神经营养因子受体的表达具有高度异质性，但它们对NTN的不同反应与Gfra1或Gfra2的表达水平无关。
