title: IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3.
abstract: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated. Recent studies showed that RTT-derived neurons have many cellular deficits when compared to control, such as: less synapses, lower dendritic arborization and reduced spine density. Interestingly, treatment of RTT-derived neurons with Insulin-like Growth Factor 1 (IGF1) could rescue some of these cellular phenotypes. Given the critical role of IGF1 during neurodevelopment, the present study used human induced pluripotent stem cells (iPSCs) from RTT and control individuals to investigate the gene expression profile of IGF1 and IGF1R on different developmental stages of differentiation. We found that the thyroid hormone receptor (TRalpha 3) has a differential expression profile. Thyroid hormone is critical for normal brain development. Our results showed that there is a possible link between IGF1/IGF1R and the TRalpha 3 and that over expression of IGF1R in RTT cells may be the cause of neurites improvement in neural RTT-derived neurons.
authors.affiliation: Department of Medicine, Laboratory of Endocrinology and Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, SP, Brazil.|Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Janaina S
authors.initials: JS
authors.lastname: de Souza
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Cassiano
authors.initials: C
authors.lastname: Carromeu
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Laila B
authors.initials: LB
authors.lastname: Torres
authors.affiliation: Department of Neurobiology and Neurosurgery, Laboratory of Neuroscience, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, SP, Brazil.
authors.forename: Bruno H S
authors.initials: BH
authors.lastname: Araujo
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Cugola
authors.affiliation: Department of Medicine, Laboratory of Endocrinology and Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, SP, Brazil.
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Alysson R
authors.initials: AR
authors.lastname: Muotri
authors.affiliation: Department of Medicine, Laboratory of Endocrinology and Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, SP, Brazil.|Departament of Biological Sciences, Universidade Federal de São Paulo, Diadema, SP, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Giannocco
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D058732:Embryoid Bodies / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D065886:Neurodevelopmental Disorders; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D013131:Spine / Q000254:growth & development / Q000473:pathology; D013569:Synapses / Q000235:genetics / Q000473:pathology; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017451:Receptors, Somatomedin; D037021:Thyroid Hormone Receptors alpha; C000622662:thyroid hormone receptor alpha, human; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1