Disease relevance of GDNF

• Developing spinal cord, superior cervical ganglion (SCG) and dorsal root ganglion (DRG) also expressed low levels of GDNF mRNA [1].
• Glial cell line-derived neurotrophic factor (GDNF) was first discovered as a potent survival factor for midbrain dopaminergic neurons and was then shown to rescue these neurons in animal models of Parkinson's disease [2].
• Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels [3].

High impact information on GDNF

• Purified recombinant GDNF promoted neurite outgrowth and survival of embryonic chick sympathetic neurons [1].
• Two days after nerve transection, GDNF mRNA levels increased dramatically in the sciatic nerve [1].
• GDNF produced robust bundle-like, fasciculated outgrowth from chick sympathetic ganglion explants [1].
• GDNF also promoted survival of about half of the neurons in embryonic chick nodose ganglion and a small subpopulation of embryonic sensory neurons in chick dorsal root and rat trigeminal ganglia [1].
• Both GDNF mRNA forms were found to be most highly expressed in developing skin, whisker pad, kidney, stomach and testis [1].

Biological context of GDNF

• Expression pattern of GDNF, c-ret, and GFRalphas suggests novel roles for GDNF ligands during early organogenesis in the chick embryo [4].
• Both a GDNF receptor signal transduction component (RET) and a binding component (GFRalpha-1 or GFRalpha-2) were independently expressed in nearby interacting tissues such as the somites, peripheral and central nervous system, and mesenchyme cells in the craniofacial region [4].
• Analysis revealed that the period from 6 to 12 days in vitro was the critical time for exposure to GDNF to generate the increase in TH-positive cell number [5].
• In older rosetted spheroids raised in absence of GDNF, rod but not cone photoreceptors underwent apoptosis [6].
• Injections of NT-4, but not GDNF, in the retina decreased the survival of ION neurons and accelerated cell death in the ION [7].

Anatomical context of GDNF

• In the present report we demonstrate that glial cell line-derived neurotrophic factor (GDNF) treatment also induces [Ca2+]i elevation by mobilizing this cation from internal stores [8].
• These findings extend the previously reported biological activities of GDNF by showing that it can act on mouse neural crest cultures to promote the development of neurons [5].
• GDNF regulates chicken rod photoreceptor development and survival in reaggregated histotypic retinal spheres [6].
• PURPOSE: To investigate the role of glial-cell-line-derived neurotrophic factor (GDNF) on proliferation, differentiation, and apoptosis of different retinal cell types--in particular, photoreceptor cells [6].
• Expression of the GDNF receptors ret and GFRalpha1 in the developing avian enteric nervous system [9].

Associations of GDNF with chemical compounds

• Retinoic acid negatively regulates GDNF and neurturin receptor expression and responsiveness in embryonic chicken sympathetic neurons [10].
• Like the members of the neurotrophin family, the GDNF-like growth factors belong structurally to the cysteine knot proteins [2].
• This analysis was undertaken because GDNF is a potent survival factor for developing motoneurons and has been shown to protect this population from ethanol neurotoxicity [11].
• Finally, the actions of GDNF are inhibited by PP2, an inhibitor of Src family tyrosine kinases, and by LY29003, an inhibitor of phosphatidylinositol 3 kinases, but not by PD98059, an inhibitor of the Erk signaling cascade [12].
• The effects of GDNF on K(Ca) channel expression in LMNs require 24 hr of continuous exposure to reach maximum and are blocked by the translation inhibitor anisomycin, indicating the need for synthesis of new proteins [12].

Other interactions of GDNF

• Unlike BDNF, neither GDNF, NT-4, nor IGF-I increased the survival of ION neurons in dissociated cultures identified by retrograde labeling with the fluorescent tracer DiI [7].
• Overlapping and specific patterns of GDNF, c-ret and GFR alpha mRNA expression in the developing chicken retina [13].
• Although GDNF displayed only low activity on survival of newborn rat SCG neurons, this protein was found to increase the expression of vasoactive intestinal peptide and preprotachykinin-A mRNAs in cultured SCG neurons [1].
• A cocktail of antibodies and binding proteins, directed against endogenous IGF-I, GDNF, and CT-1, significantly decreased mean single-twitch force [14].

Analytical, diagnostic and therapeutic context of GDNF

• We investigated the location(s), the timing, and the extent to which these GDNF receptors appear in the population of crest-derived precursors that form the avian ENS using immunohistochemistry and in situ hybridization [9].
• Recent transgenic and organ culture experiments have clearly demonstrated that GDNF is a mesenchyme-derived signaling molecule for the promotion of ureteric branching in kidney development [2].
• These analyses, using the ELISA assay, did not detect reductions in GDNF in the ethanol-exposed animals [11].

References