Responsiveness to neurturin of subpopulations of embryonic rat spinal motoneuron does not correlate with expression of GFR alpha 1 or GFR alpha 2.
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.
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.
A
A
Garcès
J
J
Livet
N
N
Grillet
C E
CE
Henderson
O
O
Delapeyrière
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins; D015870:Gene Expression; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology
D017931:DNA Primers; D029721:Drosophila Proteins; C494989:Gfra1 protein, rat; C494992:Gfra2 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D051101:Neurturin; C495057:Nrtn protein, rat; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat