title: Differential expression of the GDNF family receptors RET and GFRalpha1, 2, and 4 in subsets of motoneurons: a relationship between motoneuron birthdate and receptor expression.
abstract: Previous studies have demonstrated the expression of specific members of the glial cell line-derived neurotrophic factor (GDNF) receptor family alpha (GFRalpha) in subsets of motoneurons (MNs) in the developing mouse spinal cord. We examined the expression pattern of GFRalpha and RET in the avian lumbar spinal cord during the period of programmed cell death (PCD) of MNs by using double labeling in situ hybridization and immunohistochemistry. In the lateral motor column (LMC) of the lumbar spinal cord, a laminar organization of GFRalpha expression was observed: GFRalpha1-positive MNs were located in the medial LMC; GFRalpha1-, 2-, and 4-positive MNs were situated in the lateral LMC; and GFRalpha4-positive MNs were located in the intermediate LMC. The species of GFRalpha receptor that was expressed in MNs was found to be related to their birthdates. The expression of subpopulation-specific transcriptional factors was also used to define MNs that express a specific pattern of GFRalpha. This analysis suggests that motor pools as defined by these transcriptional factors have unique expression patterns of GFRalpha receptor. Early limb bud ablation did not affect the expression of GFRalpha in the spinal cord, indicating that regulation of receptor expression is independent of target-derived signals. Finally, GDNF mRNA expression was found in the limb during the PCD period of MNs. In conclusion, these results indicate that time of withdrawal from the mitotic cycle may specify the expression pattern of GFRalpha in subsets of MNs and that GDNF may function as a target-derived neurotrophic factor for specific subpopulations of MNs.
authors.affiliation: Department of Anatomy, School of Medicine, Fukushima Medical University, Japan. shomma@fmu.ac.jp
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Homma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaginuma
authors.forename: Sharon
authors.initials: S
authors.lastname: Vinsant
authors.forename: Miho
authors.initials: M
authors.lastname: Seino
authors.forename: Megumi
authors.initials: M
authors.lastname: Kawata
authors.forename: Thomas
authors.initials: T
authors.lastname: Gould
authors.forename: Takako
authors.initials: T
authors.lastname: Shimada
authors.forename: Nobumi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Oppenheim
mesh_terms: D000818:Animals; D017209:Apoptosis; D030161:Avian Proteins; D001717:Birds; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008161:Lumbosacral Region; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D029721:Drosophila Proteins; C113146:GFR receptor alpha 4, Gallus gallus; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila