TABLE OF CONTENTS
ABBREVIATIONS
LIST OF ORIGINAL PUBLICATIONS
SUMMARY
REVIEW OF THE LITERATURE
Neurotrophic factors
Introduction
NGF family
Neurotrophin receptors
Neurotrophins and their receptors in development and disease
GDNF family of neurotrophic factors
GDNF gene
GDNF in the nervous system
GDNF in the kidney
GDNF in other organs
Transgenic GDNF mice
Ret receptor tyrosine kinase
Ret in development
Ret in human diseases
Ret signal transduction
GDNF family receptor alphas
Development of the enteric nervous system
GDNF signaling pathway in the developing gut
Neurotrophic factors in diseases
Hirschsprung’s disease
Clinical picture
Genetics of Hirschsprung’s disease
GDNF signaling in Hirschsprung’s disease
Endothelin 3 and Endothelin Receptor B
Parkinson’s disease
GDNF in Parkinson’s
Meckel syndrome
Strategies for the identification of disease genes
Candidate genes
Mutation identification
Mutation –disease correlation
AIMS
MATERIALS AND METHODS
Cloning of human GDNF
Cloning of human and rat GFR
a
-2 cDNA
Probes
Fluorescent in situ hybridization
Northern analysis
Growth factors and antibodies
Receptor tyrosine phosphorylation assay
Sample tissues
p75NTR immunohistochemistry
In situ hybridization
RT-PCR
Cell and organ cultures
SSCP analysis
Mutation search by sequencing
Minisequencing
Radiation hybrid mapping
CFLP analysis
RESULTS AND DISCUSSION
Ret mediates GDNF signal in mesoderm induction of
Xenopus
blastula animal caps
Cloning and characterization of the GFR
a
-2 gene
Expression and function of GFR
a
-2
Distribution of GDNF and its receptors in the developing human gut
GDNF is required for ureteric budding in kidney development
p75NTR in Meckel syndrome
GDNF mutation analysis in Hirschsprung’s disease and renal agenesis
GDNF mutation analysis in Parkinson’s disease
CONCLUDING REMARKS
ACKNOWLEDGEMENTS
REFERENCES
