HE ROLE OF Ret RECEPTOR TYROSINE KINASE IN OPAMINERGIC NEURON DEVELOPMENT
نویسندگان
چکیده
bstract—Glial cell line–derived neurotrophic factor (GDNF) s one of the most potent trophic factors identified for prooting survival and function of dopaminergic (DA) neurons n the midbrain. Ret, a member of the receptor tyrosine kinase RTK) superfamily transduces GDNF signaling. The role of et in the development of DA neurons is not clear however. ere we demonstrate the involvement of Ret in the DA neuron evelopment both in vitro and in vivo. The dopamine transorter (DAT) gene was clearly induced in rat embryonic neual precursors that had been transfected with Ret. Temporary lockade of Ret expression in embryos using Ret antisense ligonucleotides (Ret-AS-ODN) in vivo led to reduced striatal A content and a decrease of tyrosine hydroxylase (TH) ositive fibers in the striatum. Additionally, some DA neurons n the substantia nigra (SN) underwent apoptotic cell death ollowing the Ret-AS-ODN treatment. Taken together, the data uggest that normal function of Ret is required in vivo for the aturation of DA neurons, in particular for cell survival and ber innervation. We further demonstrated Ret-induced exression of DAT in vitro. © 2006 IBRO. Published by Elsevier td. All rights reserved.
منابع مشابه
FMS-like Tyrosine Kinase-3 Mutation in a Child with Standard-risk ALL and Normal Karyotype
FMS-like tyrosine kinase-3 is a receptor tyrosine kinase expressed by immature hematopoietic cells and is important for the normal development of stem cells and the immune system. Mutations of FMS-like tyrosine kinase-3 have been detected in about 30% of patients with acute myelogenous leukemia and a small number of patients with acute lymphoblastic leukemia. The FMS-like tyrosine kinase-3 muta...
متن کاملIB4-Binding DRG Neurons Switch from NGF to GDNF Dependence in Early Postnatal Life
We have tested the role of glial cell line-derived neurotrophic factor (GDNF) in regulating a group of putatively nociceptive dorsal root ganglion (DRG) neurons that do not express calcitonin gene-related peptide (CGRP) and that downregulate the nerve growth factor (NGF) receptor tyrosine kinase, TrkA, after birth. We show that mRNA and protein for the GDNF receptor tyrosine kinase, Ret, are ex...
متن کاملBiphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification
The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversifica...
متن کاملRetrograde signaling onto Ret during motor nerve terminal maturation.
Establishment of the neuromuscular synapse requires bidirectional signaling between the nerve and muscle. Although much is known on nerve-released signals onto the muscle, less is known of signals important for presynaptic maturation of the nerve terminal. Our results suggest that the Ret tyrosine kinase receptor transmits a signal in motor neuron synapses that contribute to motor neuron surviv...
متن کاملEnteric Nervous System Progenitors Are Coordinately Controlled by the G Protein-Coupled Receptor EDNRB and the Receptor Tyrosine Kinase RET
The enteric nervous system (ENS) in vertebrates is derived mainly from vagal neural crest cells that enter the foregut and colonize the entire wall of the gastrointestinal tract. Failure to completely colonize the gut results in the absence of enteric ganglia (Hirschsprung's disease). Two signaling systems mediated by RET and EDNRB have been identified as critical players in enteric neurogenesi...
متن کامل