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Volume 17, Number 21,
Issue of November 1, 1997
pp. 8506-8519
Copyright ©1997 Society for Neuroscience
Neurturin and Glial Cell Line-Derived Neurotrophic Factor
Receptor- (GDNFR-), Novel Proteins Related to GDNF and GDNFR-
with Specific Cellular Patterns of Expression Suggesting Roles in the
Developing and Adult Nervous System and in Peripheral Organs
Received June 20, 1997; revised Aug. 18, 1997; accepted Aug. 25, 1997.
Johan Widenfalk1,
Christopher Nosrat1,
Andreas Tomac1, 2,
Heiner Westphal2,
Barry Hoffer3, and
Lars Olson1
1 Department of Neuroscience, Karolinska Institute,
S-171 77 Stockholm, Sweden, 2 National Institute of Child
Health and Human Development, Bethesda, Maryland 20892-2780, and
3 National Institute on Drug Abuse, National Institutes of
Health, Baltimore, Maryland 21224
Cloning strategies were used to identify a gene termed glial cell
line-derived neurotrophic factor receptor- (GDNFR-) related to
GDNFR- . In situ hybridization was then used to map
cellular expression of the GDNF-related trophic factor neurturin (NTN) and GDNFR- mRNA in developing and adult mice, and comparisons with
GDNFR- and RET were made. Neurturin is expressed in postnatal cerebral cortex, striatum, several brainstem areas, and the pineal gland. GDNFR- mRNA was more widely expressed in the developing and
adult CNS, including cerebral cortex, cerebellum, thalamus, zona
incerta, hypothalamus, brainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves. NTN
colocalized with RET and GDNFR- in ureteric buds of the developing kidney. The circular muscle layer of the developing intestines, smooth
muscle of the urether, and developing bronchiolae also expressed NTN.
GDNFR- was found in myenteric but not submucosal intestinal
plexuses. In developing salivary glands NTN had an epithelial
expression, whereas GDNFR- was expressed in surrounding tissue.
Neurturin and GDNFR- were present in developing sensory organs. In
the gonads, NTN appeared to be expressed in Sertoli cells and in the
epithelium of the oviduct, whereas GDNFR- was expressed by the germ
cell line. Our findings suggest multiple roles for NTN and GDNFR- in
the developing and adult organism. Although NTN and GDNFR-
expression patterns are sometimes complementary, this is not always the
case, suggesting multiple modi operandi of GDNF and NTN in relation to
RET and the two binding proteins, GDNFR- and GDNFR-.
Key words:
GDNF;
neurturin;
GDNFR-;
GDNFR-;
RET;
in
situ hybridization;
CNS;
development;
kidney;
gastrointestinal
tract;
gonads;
kainic acid;
GFR-1;
GFR-2
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