Premium
110 Roles of gdnf in the development of nervous system and kidney
Author(s) -
Saarma Mart,
Arumäe Urmas,
Suvanto Petro,
Lindahl Maria,
Sainio Kirsi,
Sariola Hannu
Publication year - 1996
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(96)80300-5
Subject(s) - citation , library science , glial cell line derived neurotrophic factor , computer science , medicine , receptor , neurotrophic factors
Glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor B superfamily supports the survival of different populations of neurons in the peripheral and central nervous system. and may have therapeutic applications in neurodegenerative disorders. We have studied the expression patterns of GDNF mRNA and the role of GDNF in developing rat embryo. In situ hytnidization data reveal abundant expression of GDNF mRNA in the muscle layer of developing digestive tracL skeletal muscle and developing cartilage. High expression was also confined to urogenital tract, culminating in Ihe expression of GDNF in the condensing mesenchyme of metanephric kidney. In organotypic culture radiolabelled GDNF binds to the neurons of tie enteric nervous system and to Ihe tips of the branching ureter buds of the developing kidney. Functional assays with GDNF-coupled microbeads and antisense oligonucleotide inhibition studies in organotypic cultures show that GDNF is a ureter bud branching factor for developing kidney and diiferentiation/survival factor for developing peripheral neurons. We have also found that GDNF binds to and activates a orphan receptor t)Tosine kinase. Our results show that this orphan RTK is a functional GDNF receptor mediating aI least some of the signal transduction processes mitiated by GDNF binding. III