Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat
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Choi-Lundberg, DL and Bohn, MC, Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat, Developmental Brain Research, 85, (1) pp. 80-88. ISSN 0165-3806 (1995) [Refereed Article]
Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta family isolated from the rat glial tumor cell line, B49. In embryonic dopaminergic (DA) neurons in vitro, GDNF promotes survival, high-affinity dopamine uptake, and neurite outgrowth. We have used a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific to GDNF to study the developmental expression of GDNF mRNA in central nervous system (CNS) and peripheral organs of embryonic rat on gestational days E11.5, E13.5 and E18, neonatal rat on postnatal days P0 and P10, and adult rat. GDNF mRNA is expressed throughout the CNS, with highest levels in P0 spinal cord and in P0 and P10 striatum. Lower levels are present in the brainstem (including the ventral mesencephalon, which contains the DA neurons of the substantia nigra), cerebellum, diencephalon, and telencephalon, as well as in primary cultures of cerebellar granule cells prepared from P7 cerebellum and astrocytes prepared from P1 cortex. The cerebellum has an unusual temporal pattern of expression, high at birth and in the adult, but undetectable at P10. GDNF mRNA is also expressed in many peripheral tissues at higher levels than in brain. These include embryonic limb bud, kidney and gut; neonatal kidney, gut, lung and testis; and adult lung, liver and ovary. In addition to the predicted RT-PCR product, we also observed a minor band which was shown to be identical to GDNF in the mature peptide sequence, but which has a 78 base pair deletion in the preproprotein sequence. This shortened form of GDNF mRNA has an essentially identical pattern of distribution as GDNF and may represent an alternatively spliced form. A homologous short form of GDNF mRNA was also amplified from human fetal astrocytes. These observations suggest that GDNF may be a target derived and/or locally acting neurotrophic factor for other classes of CNS neurons, as well as for DA neurons of the substantia nigra. Additionally, GDNF likely plays a role as a neurotrophic factor in the perpheral nervous system and/or serves as a growth factor for non-neuronal cells. © 1995 Elsevier Science B.V. All rights reserved.
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