Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Malas, Stavros; Postlethwaite, Michael; Ekonomou, Antigoni; Whalley, Benjamin J.; Nishiguchi, Seiji; Wood, Heather; Meldrum, Brian S.; Constanti, Andrew; Episkopou, Vasso

doi:10.1016/s0306-4522(03)00158-1

Cited by 55 publications

(63 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further bioinformatic analysis indicated that selective occupation by either factor is restricted to genes that are predominantly expressed in late populations of neurons and glia. This correlates with the finding that SoxB1 factors eventually reappear during late phases of neurogenesis in select and largely nonoverlapping populations of mature neurons, where they perform functions that are unrelated to the earlier ones in NPCs (Malas et al 2003;Ferri et al 2004).…”

Section: Sequential Enhancer Occupancy By Sox Proteins During Neurogesupporting

confidence: 85%

SOX after SOX: SOXession regulates neurogenesis: Figure 1.

Wegner¹

2011

Genes Dev.

View full text Add to dashboard Cite

Vertebrate embryonic stem (ES) cells give rise to many different cell types in multistep processes. These involve the establishment of a competent state, specification, differentiation, and maturation, and often involve Sox transcription factors. In this issue of Genes & Development, Bergsland and colleagues (pp. 2453–2464) determine the genome-wide binding profile of Sox2, Sox3, and Sox11 as ES cells become specified to neural precursors and differentiate into neurons. An ordered, sequential binding of these Sox proteins to a common set of gene enhancers was found to drive neurogenesis, as Sox proteins first help to preselect neural genes in ES cells and later ensure their proper activation in neural precursors or neurons.

show abstract

Section: Sequential Enhancer Occupancy By Sox Proteins During Neurogesupporting

confidence: 85%

SOX after SOX: SOXession regulates neurogenesis: Figure 1.

Wegner¹

2011

Genes Dev.

View full text Add to dashboard Cite

show abstract

“…Members of the SOXB1 subgroup (SOX1, SOX2, and SOX3) were found to be important in directing the early development of neural tissue, whereas SOX9 and SOX21 were involved in late neuronal development. Interestingly, Sox1 -/-mice are characterized by epilepsy [22], which is also known to affect 20%-25% of FXS patients. In addition, patients with SOX3 deficiency show symptoms similar to those observed in FXS patients, characterized by intellectual disability [23,24].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Telias

Mayshar

Amit

et al. 2015

Stem Cells and Development

View full text Add to dashboard Cite

Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the ''GSK3b theory of FXS'' for the first time in a human-based model. We found no evidence for a pathological increase in GSK3b protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system.

show abstract

“…A model reconciling both scenarios has been proposed whereby SOX1 plays an initial role in maintenance of division in the progenitor pool, but, upon continued expression, leads to neuronal differentiation (Kan et al, 2007). Loss of SOX1 is largely compensated by SOX2 and SOX3 during development, but leads to epilepsy and eventual lethality (Wegner, 1999;Malas et al, 2003;Graham et al, 2003;Kan et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Sox1 marks an activated neural stem/progenitor cell in the hippocampus

et al. 2012

View full text Add to dashboard Cite

SUMMARYThe dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born granular neurons, as well as a small number of mature hilar astrocytes. Furthermore, a subpopulation of Sox1-marked cells have long-term neurogenic potential, producing new neurons 3 months after inactivation of tetracycline transactivator. Remarkably, after 8 weeks of labeling and a 12-week chase, as much as 44% of all granular neurons in the dentate gyrus were derived from Sox1 lineagetraced adult neural stem/progenitor cells. The fraction of Sox1-positive cells within the radial astrocyte population decreases with age, correlating with a decrease in neurogenesis. However, expression profiling shows that these cells are transcriptionally stable throughout the lifespan of the mouse. These results demonstrate that Sox1 is expressed in an activated stem/progenitor population whose numbers decrease with age while maintaining a stable molecular program.

show abstract

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Cited by 55 publications

References 52 publications

SOX after SOX: SOXession regulates neurogenesis: Figure 1.

SOX after SOX: SOXession regulates neurogenesis: Figure 1.

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Sox1 marks an activated neural stem/progenitor cell in the hippocampus

Contact Info

Product

Resources

About