An-Najah Blogs :: Belal Mahmoud M. Rahhal An-Najah Blogs :: Belal Mahmoud M. Rahhal en-us Mon, 26 Oct 2020 15:12:13 IST Mon, 26 Oct 2020 15:12:13 IST In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis ArticlesNeurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth survival and maturation of neuronal phenotypes in the central and peripheral nervous system Previous studies have suggested that TGF- plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors most strikingly of GDNF To test the physiological relevance of this finding TGF-2GDNF double mutant d-ko mice were generated Double mutant mice die at birth like single mutants due to kidney agenesis GDNF and congential cyanosis TGF-2 respectively To test for the in vivo relevance of TGF-2GDNF cooperativity to regulate neuron survival mesencephalic dopaminergic neurons lumbar motoneurons as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E185 A partial reduction in neuron numbers was observed in lumbar motoneurons sensory and sympathetic neurons in GDNF single mutants which was further reduced in TGF-2GDNF double mutant mice at E185 However TGF-2 single mutant mice showed no loss of neurons These data point towards a cooperative role of TGF-2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated International Journal of Developmental Neuroscience Volume 27 Issue 1 February 2009 Pages 97-102 http:dxdoiorg101016jijdevneu200808003Transforming growth factor beta cooperates with persephin for dopaminergic phenotype induction. Articles1: Stem Cells 2008 Jul;267:1683-94 Epub 2008 Apr 17 Transforming growth factor beta cooperates with persephin for dopaminergic phenotype induction Roussa E Oehlke O Rahhal B Heermann S Heidrich S Wiehle M Krieglstein K aDepartment for Neuroanatomy Georg-August-University Goettingen Goettingen Germany eroussa@gwdgde The aim of the present study was to investigate the putative cooperative effects of transforming growth factor beta TGF-beta and glial cell line-derived neurotrophic factor GDNF family ligands in the differentiation of midbrain progenitors toward a dopaminergic phenotype Therefore a mouse midbrain embryonic day E 12 neurospheres culture was used as an experimental model We show that neurturin and persephin PSPN but not GDNF are capable of transient induction of dopaminergic neurons in vitro This process however requires the presence of endogenous TGF-beta In contrast after 8 days in vitro GDNF rescued the TGF-beta neutralization-dependent loss of the TH-positive cells In vivo at E145 no apparent phenotype concerning dopaminergic neurons was observed in Tgf-beta2--gdnf-- double mutant mice In vitro combined TGF-betaPSPN treatment achieved a yield of approximately 20 TH-positive cells that were less vulnerable against 1-methyl-4-phenyl pyridinium ion toxicity The underlying TGF-betaPSPN differentiation signaling is receptor-mediated involving p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways These results indicate that phenotype induction and survival of fully differentiated neurons are accomplished through distinct pathways and individual factor requirement TGF-beta is required for the induction of dopaminergic neurons whereas GDNF is required for regulating andor maintaining a differentiated neuronal phenotype Moreover this study suggests that the combination of TGF-beta with PSPN is a potent inductive cocktail for the generation of dopaminergic neurons that should be considered in tissue engineering and cell replacement therapies for Parkinsons disease PMID: 18420832 [PubMed - indexed for MEDLINE] Isoform-specific role of transforming growth factor-beta2 in the regulation of proliferation and differentiation of murine adrenal chromaffin cells in vivo. Articles1: J Neurosci Res 2004 Nov 15;784:493-8 Isoform-specific role of transforming growth factor-beta2 in the regulation of proliferation and differentiation of murine adrenal chromaffin cells in vivo Rahhal B Dnker N Combs S Krieglstein K Department of Neuroanatomy Medical Faculty University Goettingen D-37075 Goettingen Germany Chromaffin cells the neuroendocrine cells of the adrenal medulla play an important role in molecular cellular and developmental neurobiology Unlike the closely related sympathetic neurons chromaffin cells are able to proliferate throughout their whole life span Proliferation of chromaffin cells in vivo is thought to be regulated by the interaction of neurogenic and hormonal signals Previous studies have shown that chromaffin cells synthesize and release transforming growth factor-betas TGF-betas In the present study effects of TGF-betas on proliferation and differentiation of chromaffin cells in mouse adrenal chromaffin cells were investigated in a genetic mouse model We observed a significant increase in the total number of tyrosine hydroxylase-positive TH cells in Tgfbeta2-- knockout mouse embryos at embryonic day E 185 compared with wild-type animals Tgfbeta2 but no changes in the number of TH cells were observed in Tgfbeta3-- mouse mutants At E155 but not at E185 there was a marked increase in the number of proliferative cell nuclear antigen-positive chromaffin cells in Tgfbeta2-- knockout embryos compared with the wild-type group On the other hand there was a clear decrease in the ratio of total number of phenylethanolamine-N-methyltransferase-positive cells to the total TH in Tgfbeta2-- mice embryos at E185 compared with wild-type animals This is the first documentation of the physiological significance of the TGF-beta2 an isoform that has been suggested to play a role in the regulation of chromaffin cells proliferation and differentiation based on in vitro experiments PMID: 15478122 [PubMed - indexed for MEDLINE]