Sox2 Acts in Thalamic Neurons to Control the Development of Retina-Thalamus-Cortex Connectivity

Mercurio, Sara; Serra, Linda; Motta, Alessia; Gesuita, Lorenzo; Sánchez-Arrones, Luisa; Inverardi, Francesca; Foglio, Benedetta; Barone, Cristiana; Kaimakis, Polynikis; Martynoga, Ben; Ottolenghi, Sergio; Studer, Michèle; Guillemot, François; Frassoni, Carolina; Bovolenta, Paola; Nicolis, Silvia K.

doi:10.1016/j.isci.2019.04.030

Cited by 34 publications

(58 citation statements)

References 41 publications

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“…Recently, the role of Sox2 in the neuronal development of these sensory thalamic nuclei has been investigated by means of conditional thalamic ablation within post-mitotic neurons. Particular attention has been given to the role of Sox2 in the dLGN and on how its thalamic ablation influences the development of the visual system [35].…”

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

“…Neurons in the dLGN receive input from the retina and project to the visual cortex. Projections from the dLGN to the visual cortex are required for the correct patterning of the visual cortex, if projections from dLGN neurons to the cortex are reduced/absent, the primary visual cortex and the adjacent higher order visual cortical areas are not correctly defined [35,63]. Sox2 deletion in these dLGN neurons, when they are already post-mitotic (by means of a thalamus specific Cre recombinase (Rorα-Cre expressed from E14.5)), results in a reduction of the size of the dLGN postnatally (Figure 2A).…”

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

“…Neurons in the VP also appear to require Sox2 for their correct development since their projections to the somatosensory cortex are reduced in Sox2 thalamic mutants and not correctly organized. On the other hand, projections from the MG to the auditory cortex appear less affected by Sox2 loss in the same thalamic mutants described above, but their development should be studied in more detail to properly address Sox2 requirement [35].…”

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

“…In fact, ephrin-A5 (efna5) was found to be downregulated in the Sox2 mutant dLGN, even at stages preceding the misrouting phenotype. It is thought that Efna5 could be a direct Sox2 target since Sox2 binding sites were identified in an intron, that behaves as an enhancer activated by Sox2 in in vitro co-transfection assays [18,35].…”

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

“…Serotonin uptake by dLGN neurons is affected in the thalamic Sox2 cKO, since expression of the serotonin transporters, SERT and vMAT, is strongly downregulated in the mutant dLGN. As a consequence (at least in part) of this, the amount of serotonin-positive fibers reaching the visual cortex is greatly reduced [35].…”

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

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More than just Stem Cells: Functional Roles of the Transcription Factor Sox2 in Differentiated Glia and Neurons

Mercurio

Serra

Nicolis

2019

IJMS

Self Cite

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The Sox2 transcription factor, encoded by a gene conserved in animal evolution, has become widely known because of its functional relevance for stem cells. In the developing nervous system, Sox2 is active in neural stem cells, and important for their self-renewal; differentiation to neurons and glia normally involves Sox2 downregulation. Recent evidence, however, identified specific types of fully differentiated neurons and glia that retain high Sox2 expression, and critically require Sox2 function, as revealed by functional studies in mouse and in other animals. Sox2 was found to control fundamental aspects of the biology of these cells, such as the development of correct neuronal connectivity. Sox2 downstream target genes identified within these cell types provide molecular mechanisms for cell-type-specific Sox2 neuronal and glial functions. SOX2 mutations in humans lead to a spectrum of nervous system defects, involving vision, movement control, and cognition; the identification of neurons and glia requiring Sox2 function, and the investigation of Sox2 roles and molecular targets within them, represents a novel perspective for the understanding of the pathogenesis of these defects.

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Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

Section: Sox2 Functions In Differentiated Glia and Neuronsmentioning

confidence: 99%

See 3 more Smart Citations

More than just Stem Cells: Functional Roles of the Transcription Factor Sox2 in Differentiated Glia and Neurons

Mercurio

Serra

Nicolis

2019

IJMS

Self Cite

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METTL3 relieved the injury of SH‐SY5Y cells treated with lipopolysaccharide and exposed to sevoflurane through regulating the m6A levels of Sox2

Wang

Yang

2023

Brain and Behavior

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Introduction: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients. The objective of this study was to investigate the role of methyltransferase 3 (METTL3) in the POCD progression. Methods: The SH-SY5Y cells were treated with lipopolysaccharide (LPS) and exposed to sevoflurane to establish a POCD cell model. The cell viability and proliferation were assessed with MTT and EdU assays. Besides, the cell apoptosis was determined with TUNEL staining and flow cytometry. Additionally, the inflammatory factors were measured with ELISA. N6-methyladenosine (m6A) RNA Methylation Quantification Kit was used to detect the m6A levels. The relative expressions of methyltransferase 3 (METTL3) and Sex-determining region Y-box-2 (Sox2) was measured with RT-qPCR and western blot assays. RNA methylation immunoprecipitation-real-time quantitative PCR was performed to detect the RNA that was m6A modified. Results: After LPS treatment and sevoflurane exposure, the cell viability and proliferation were decreased and the cell apoptosis was elevated. The m6A and the METTL3 expression levels in the POCD cell model were declined. METTL3 overexpression promoted the cell growth and inhibited the cell apoptosis in the POCD cell model. Besides, the Sox2 levels were reduced in the POCD cell model. METTL3 silencing declined the m6A and mRNA levels of Sox2, while overexpression of METTL3 elevated it. The relationship between METTL3 and Sox2 was confirmed with double luciferase assay. Finally, Sox2 silencing neutralized the role of METTTL3 overexpression in the POCD cell model. Conclusion: METTL3 relieved the injury of the SH-SY5Y cells induced by LPS treatment and sevoflurane exposure through regulating the m6A and mRNA levels of Sox2.

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Oligodendrocyte origin and development in the zebrafish visual system

Santos-Ledo

Pérez-Montes

DeOliveira-Mello

et al. 2022

J of Comparative Neurology

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Oligodendrocytes are the myelinating cells in the central nervous system. In birds and mammals, the oligodendrocyte progenitor cells (OPCs) originate in the preoptic area (POA) of the hypothalamus. However, it remains unclear in other vertebrates such as fish. Thus, we have studied the early progression of OPCs during zebrafish visual morphogenesis from 2 days post fertilization (dpf) until 11 dpf using the olig2:EGFP transgenic line; and we have analyzed the differential expression of transcription factors involved in oligodendrocyte differentiation: Sox2 (using immunohistochemistry) and Sox10 (using the transgenic line sox10:tagRFP). The first OPCs (olig2:EGFP/Sox2) were found at 2 dpf in the POA. From 3 dpf onwards, these olig2:EGFP/Sox2 cells migrate to the optic chiasm, where they invade the optic nerve (ON), extending toward the retina. At 5 dpf, olig2:EGFP/Sox2 cells in the ON also colocalize with sox10:tagRFP. When olig2:EGFP cells differentiate and present more projections, they become positive only for sox10:tagRFP. olig2:EGFP/sox10: tagRFP cells ensheath the ON by 5 dpf when they also become positive for a myelin marker, based on the mbpa:tagRFPt transgenic line. We also found olig2:EGFP cells in other regions of the visual system. In the central retina at 2 dpf, they are positive for Sox2 but later become restricted to the proliferative germinal zone without this marker. In the ventricular areas of the optic tectum, olig2:EGFP cells present Sox2 but arborized ones sox10:tagRFP instead. Our data matches with other models, where OPCs are specified in the POA and migrate to the ON through the optic chiasm.

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Sox2 Acts in Thalamic Neurons to Control the Development of Retina-Thalamus-Cortex Connectivity

Cited by 34 publications

References 41 publications

More than just Stem Cells: Functional Roles of the Transcription Factor Sox2 in Differentiated Glia and Neurons

More than just Stem Cells: Functional Roles of the Transcription Factor Sox2 in Differentiated Glia and Neurons

METTL3 relieved the injury of SH‐SY5Y cells treated with lipopolysaccharide and exposed to sevoflurane through regulating the m6A levels of Sox2

Oligodendrocyte origin and development in the zebrafish visual system

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