Sox11 neuron

Transcription factor 4 (TCF4) is a critical regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability, and schizophrenia. As a class I bHLH transcription factor it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we aim to identify transcription factor (TF) partners of TCF4 in the control of interhemispheric connectivity formation. Using a new bioinformatic strategy integrating TF expression levels and regulon activities from single cell RNA-sequencing data, we find evidence that TCF4 interacts with non-bHLH TFs and modulates their transcriptional activity in Satb2+ intercortical projection neurons...

The role of protein stabilization in cortical development remains poorly understood. A recessive mutation in the USP11 gene is found in a rare neurodevelopmental disorder with intellectual disability, but its pathogenicity and molecular mechanism are unknown. Here, we show that mouse Usp11 is expressed highly in embryonic cerebral cortex, and Usp11 deficiency impairs layer 6 neuron production, delays late-born neuronal migration, and disturbs cognition and anxiety behaviors. Mechanistically, these functions are mediated by a previously unidentified Usp11 substrate, Sox11...

The failure of adult CNS neurons to survive and regenerate their axons after injury or in neurodegenerative disease remains a major target for basic and clinical neuroscience. Recent data demonstrated in the adult mouse that exogenous expression of Sry-related high-mobility-box 11 (Sox11) promotes optic nerve regeneration after optic nerve injury, but exacerbates the death of a subset of retinal ganglion cells, alpha-RGCs. During development, Sox11 is required for RGC differentiation from retinal progenitor cells (RPCs), and we found that mutation of a single residue to prevent sumoylation at lysine 91 (K91) increased nuclear localization and RGC differentiation in vitro Here we explored whether this Sox11 manipulation similarly has stronger effects on RGC survival and optic nerve regeneration...

CONTEXT.—: Primitive neuroectodermal tumors (PNETs) may arise as a somatic-type malignancy in germ cell tumors. In this setting, most PNETs resemble those of the central nervous system and lack chromosome 22 translocations. However, description of the morphologic and differentiation spectrum of PNETs arising from germ cell tumors is lacking. OBJECTIVE.—: To investigate the morphologic and immunohistochemical features of these tumors, concentrating on neuronal and glial features...

Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6-8 weeks old) mice, the developmental TF SOX11 is induced in neurons within 6 h either by electroconvulsive stimulation or by exploration of a novel environment...

Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. We sought to identify the transcription factors exhibiting altered and subtype-specific expression patterns in B-ALL and report here that SOX11, a developmental and neuronal transcription factor, is aberrantly expressed in the ETV6-RUNX1 and TCF3-PBX1 subtypes of acute B-cell leukemias. We show that a high expression of SOX11 leads to alterations of gene expression that are typically associated with cell adhesion, migration, and differentiation...

Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down)...

EED (embryonic ectoderm development) is a core component of the Polycomb repressive complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27) during the process of self-renewal, proliferation, and differentiation of embryonic stem cells. However, its function in the mammalian nervous system remains unexplored. Here, we report that loss of EED in the brain leads to postnatal lethality, impaired neuronal differentiation, and malformation of the dentate gyrus. Overexpression of Sox11, a downstream target of EED through interaction with H3K27me1, restores the neuronal differentiation capacity of EED-ablated neural stem/progenitor cells (NSPCs)...

The SOXC transcription factors Sox4, Sox11, and Sox12, are critical neurodevelopmental regulators that are thought to function in a highly redundant fashion. Surprisingly, heterozygous missense mutations or deletions of SOX11 were recently detected in patients with Coffin-Siris syndrome like syndrome (CSSLS), a neurodevelopmental disorder associated with intellectual disability, demonstrating that in humans SOX11 haploinsufficiency cannot be compensated and raising the question of the function of SOX11 in human neurodevelopment...

Interstitial deletions within the chromosomal region 2q24.2 have already been linked to intellectual disability (ID) in the past. In most cases the described patients showed a syndromic form of ID associated with large deletions containing multiple genes. Here we describe a family with two siblings with mild non-syndromic ID. They shared the same 564 kb deletion in the chromosomal region 2q24.2 containing only the TANK gene, which was inherited from the similarly affected father, thus suggesting haploinsufficiency of TANK as a novel cause of non-syndromic ID...

Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular basis of brain pathology in prion disease. Temporal profiles in two mouse models of prion disease, bovine spongiform encephalopathy (BSE) and a mouse-adapted strain of scrapie (RML) were performed in microdissected regions of the CA1 hippocampus and granular layer of the cerebellum which are both enriched in neuronal cell bodies...

In mammals, neurons in the peripheral nervous system (PNS) have regenerative capacity following injury, but it is generally absent in the CNS. This difference is attributed, at least in part, to the intrinsic ability of PNS neurons to activate a unique regenerative transcriptional program following injury. Here, we profiled gene expression following sciatic nerve crush in mice and identified long noncoding RNAs (lncRNAs) that act in the regenerating neurons and which are typically not expressed in other contexts...

The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11's activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11's transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133...

AIM: Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor. METHODS: Overexpression of transcription factor SRY (sex determining region Y)-box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection...

Axon regeneration in the central nervous system is prevented in part by a developmental decline in the intrinsic regenerative ability of maturing neurons. This loss of axon growth ability likely reflects widespread changes in gene expression, but the mechanisms that drive this shift remain unclear. Chromatin accessibility has emerged as a key regulatory mechanism in other cellular contexts, raising the possibility that chromatin structure may contribute to the age-dependent loss of regenerative potential. Here we establish an integrated bioinformatic pipeline that combines analysis of developmentally dynamic gene networks with transcription factor regulation and genome-wide maps of chromatin accessibility...

The high-mobility-group domain containing SoxC transcription factors Sox4 and Sox11 are expressed and required in the vertebrate central nervous system in neuronal precursors and neuroblasts. To identify genes that are widely regulated by SoxC proteins during vertebrate neurogenesis we generated expression profiles from developing mouse brain and chicken neural tube with reduced SoxC expression and found the transcription factor prospero homeobox protein 1 (Prox1) strongly down-regulated under both conditions...

The peripherally projecting axons of dorsal root ganglion (DRG) neurons readily regenerate after damage while their centrally projecting branches do not regenerate to the same degree after injury. One important reason for this inconsistency is the lack of pro-regeneration gene expression that occurs in DRG neurons after central injury relative to peripheral damage. The transcription factor SRY-box-containing gene 11 (Sox11) may be a crucial player in the regenerative capacity of axons as previous evidence has shown that it is highly upregulated after peripheral axon damage but not after central injury...

Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability...

In both the central nervous system (CNS) and the peripheral nervous system (PNS), axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11 . Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i) the acutely injured CNS (retina after optic nerve crush) and PNS (dorsal root ganglion after sciatic nerve crush), (ii) a CNS regeneration model (retina after optic nerve crush and induced regeneration); and (iii) the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model)...

During development, generation of neurons is coordinated by the sequential activation of gene expression programs by stage- and subtype-specific transcription factor networks. The SoxC group transcription factors, Sox4 and Sox11, have recently emerged as critical components of this network. Initially identified as survival and differentiation factors for neural precursors, SoxC factors have now been linked to a broader array of developmental processes including neuronal subtype specification, migration, dendritogenesis and establishment of neuronal projections, and are now being employed in experimental strategies for neuronal replacement and axonal regeneration in the diseased central nervous system...