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https://www.readbyqxmd.com/read/29786967/developmental-chromatin-restriction-of-pro-growth-gene-networks-acts-as-an-epigenetic-barrier-to-axon-regeneration-in-cortical-neurons
#1
Ishwariya Venkatesh, Vatsal Mehra, Zimei Wang, Ben Califf, Murray G Blackmore
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...
May 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29749639/the-homeodomain-transcription-factor-prox1-is-a-direct-target-of-soxc-proteins-during-developmental-vertebrate-neurogenesis
#2
Anne Jacob, Hannah M Wüst, Johannes M Thalhammer, Franziska Fröb, Melanie Küspert, Simone Reiprich, Elli-Anna Balta, D Chichung Lie, Michael Wegner, Elisabeth Sock
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 Prox1 strongly downregulated under both conditions. This led us to hypothesize that Prox1 expression depends on SoxC proteins in the developing central nervous system of mouse and chicken...
May 11, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29746989/increased-expression-of-transcription-factor-sry-box-containing-gene-11-sox11-enhances-neurite-growth-by-regulating-neurotrophic-factor-responsiveness
#3
Michael P Jankowski, Lauren Miller, H Richard Koerber
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...
May 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29459770/polycomb-protein-family-member-cbx7-regulates-intrinsic-axon-growth-and-regeneration
#4
Run-Shan Duan, Gang-Bin Tang, Hong-Zhen Du, Yi-Wen Hu, Pei-Pei Liu, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Rui-Ying Wang, Zhao-Qian Teng, Chang-Mei Liu
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...
February 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29209164/differential-expression-of-sox11-and-bdnf-mrna-isoforms-in-the-injured-and-regenerating-nervous-systems
#5
Felix L Struebing, Jiaxing Wang, Ying Li, Rebecca King, Olivia C Mistretta, Arthur W English, Eldon E Geisert
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)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29079881/soxc-transcription-factors-multifunctional-regulators-of-neurodevelopment
#6
REVIEW
Atria Kavyanifar, Soeren Turan, D Chichung Lie
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...
January 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/28641113/enhanced-functional-genomic-screening-identifies-novel-mediators-of-dual-leucine-zipper-kinase-dependent-injury-signaling-in-neurons
#7
Derek S Welsbie, Katherine L Mitchell, Vinod Jaskula-Ranga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E Martin, Ping-Wu Zhang, Yan Ge, Yukan Duan, John Fuller, Byung-Jin Kim, Eman Hamed, Xitiz Chamling, Lei Lei, Iain D C Fraser, Ze'ev A Ronai, Cynthia A Berlinicke, Donald J Zack
Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641110/sox11-expression-promotes-regeneration-of-some-retinal-ganglion-cell-types-but-kills-others
#8
Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, Zhigang He
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641102/live-or-die-depends-on-who-you-are
#9
Takaaki Kuwajima, Carol Mason
In this issue of Neuron, Welsbie et al. (2017) and Norsworthy et al. (2017) implicate the transcription factor Sox11 as a key player after optic nerve injury-in DLK signaling of RGC cell death, and in RGC regeneration and survival but only in certain RGCs.
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28411269/novel-regulatory-mechanisms-for-the-soxc-transcriptional-network-required-for-visual-pathway-development
#10
Kun-Che Chang, Jonathan Hertz, Xiong Zhang, Xiao-Lu Jin, Peter Shaw, Brooke A Derosa, Janet Y Li, Praseeda Venugopalan, Daniel A Valenzuela, Roshni D Patel, Kristina R Russano, Shomoukh A Alshamekh, Catalina Sun, Kevin Tenerelli, Chenyi Li, Dmitri Velmeshev, Yuyan Cheng, Timothy M Boyce, Alexandra Dreyfuss, Mohammed S Uddin, Kenneth J Muller, Derek M Dykxhoorn, Jeffrey L Goldberg
What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system...
May 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193280/functional-role-of-alk-related-signal-cascades-on-modulation-of-epithelial-mesenchymal-transition-and-apoptosis-in-uterine-carcinosarcoma
#11
H Inoue, M Hashimura, M Akiya, R Chiba, M Saegusa
BACKGROUND: Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Recently, the deregulated expression of full-length ALK has been observed in some primary solid tumors, but little is known about its involvement in the tumorigenesis of uterine carcinosarcomas (UCSs). Here we examined the functional role of the ALK gene in UCSs. METHODS: Regulation and function of the ALK gene were assessed using two endometrial carcinoma cell lines...
February 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28053041/lhx2-interacts-with-the-nurd-complex-and-regulates-cortical-neuron-subtype-determinants-fezf2-and-sox11
#12
Bhavana Muralidharan, Zeba Khatri, Upasana Maheshwari, Ritika Gupta, Basabdatta Roy, Saurabh J Pradhan, Krishanpal Karmodiya, Hari Padmanabhan, Ashwin S Shetty, Chinthapalli Balaji, Ullas Kolthur-Seetharam, Jeffrey D Macklis, Sanjeev Galande, Shubha Tole
In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909100/lhx2-interacts-with-the-nurd-complex-and-regulates-cortical-neuron-subtype-determinants-fezf2-and-sox11
#13
Bhavana Muralidharan, Zeba Khatri, Upasana Maheshwari, Ritika Gupta, Basabdatta Roy, Saurabh J Pradhan, Krishanpal Karmodiya, Hari Padmanabhan, Ashwin Shetty, Chinthapalli Balaji, Ullas Kolthur-Seetharam, Jeffrey D Macklis, Sanjeev Galande, Shubha Tole
In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor Lhx2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that Lhx2 binds to the NuRD histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27225775/optogenetic-interrogation-of-functional-synapse-formation-by-corticospinal-tract-axons-in-the-injured-spinal-cord
#14
Naveen Jayaprakash, Zimei Wang, Brian Hoeynck, Nicholas Krueger, Audra Kramer, Eric Balle, Daniel S Wheeler, Robert A Wheeler, Murray G Blackmore
UNLABELLED: To restore function after injury to the CNS, axons must be stimulated to extend into denervated territory and, critically, must form functional synapses with appropriate targets. We showed previously that forced overexpression of the transcription factor Sox11 increases axon growth by corticospinal tract (CST) neurons after spinal injury. However, behavioral outcomes were not improved, raising the question of whether the newly sprouted axons are able to form functional synapses...
May 25, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27225767/sox11-balances-dendritic-morphogenesis-with-neuronal-migration-in-the-developing-cerebral-cortex
#15
Yoshio Hoshiba, Tomohisa Toda, Haruka Ebisu, Mayu Wakimoto, Shigeru Yanagi, Hiroshi Kawasaki
UNLABELLED: The coordinated mechanisms balancing promotion and suppression of dendritic morphogenesis are crucial for the development of the cerebral cortex. Although previous studies have revealed important transcription factors that promote dendritic morphogenesis during development, those that suppress dendritic morphogenesis are still largely unknown. Here we found that the expression levels of the transcription factor Sox11 decreased dramatically during dendritic morphogenesis. Our loss- and gain-of-function studies using postnatal electroporation and in utero electroporation indicate that Sox11 is necessary and sufficient for inhibiting dendritic morphogenesis of excitatory neurons in the mouse cerebral cortex during development...
May 25, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27185484/developmental-exposure-to-2-3-7-8-tetrachlorodibenzo-p-dioxin-may-alter-lh-release-patterns-by-abolishing-sex-differences-in-gaba-glutamate-cell-number-and-modifying-the-transcriptome-of-the-male-anteroventral-periventricular-nucleus
#16
Javier Del Pino Sans, Kelsey J Clements, Alexander Suvorov, Sudha Krishnan, Hillary L Adams, Sandra L Petersen
Developmental exposure to arylhydrocarbon receptor (AhR) ligands abolishes sex differences in a wide range of neural structures and functions. A well-studied example is the anteroventral periventricular nucleus (AVPV), a structure that controls sex-specific luteinizing hormone (LH) release. In the male, testosterone (T) secreted by the developing testes defeminizes LH release mechanisms; conversely, perinatal AhR activation by 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) blocks defeminization. To better understand developmental mechanisms altered by TCDD exposure, we first verified that neonatal TCDD exposure in male rats prevented the loss of AVPV GABA/glutamate neurons that are critical for female-typical LH surge release...
August 4, 2016: Neuroscience
https://www.readbyqxmd.com/read/26962049/cross-species-functional-analyses-reveal-shared-and-separate-roles-for-sox11-in-frog-primary-neurogenesis-and-mouse-cortical-neuronal-differentiation
#17
Chao Chen, Jing Jin, Garrett A Lee, Elena Silva, Maria Donoghue
A well-functioning brain requires production of the correct number and types of cells during development; cascades of transcription factors are essential for cellular coordination. Sox proteins are transcription factors that affect various processes in the development of the nervous system. Sox11, a member of the SoxC family, is expressed in differentiated neurons and supports neuronal differentiation in several systems. To understand how generalizable the actions of Sox11 are across phylogeny, its function in the development of the frog nervous system and the mouse cerebral cortex were compared...
2016: Biology Open
https://www.readbyqxmd.com/read/26857655/the-transcriptional-coregulator-maml1-affects-dna-methylation-and-gene-expression-patterns-in-human-embryonic-kidney-cells
#18
Milica Putnik, David Brodin, Tomasz K Wojdacz, Fredrik Fagerström-Billai, Karin Dahlman-Wright, Annika E Wallberg
Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular and urogenital. The present study aimed to explore the genome wide effects of MAML1 on DNA methylation and RNA expression in human embryonic kidney cells. Infinium HumanMethylation450 BeadChip Illumina array, methylation-sensitive high-resolution melt technique, Chip Analysis Methylation Pipeline and RNA profiling approaches were used to study MAML1 effects on the epigenome...
March 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/26203155/orchestration-of-neuronal-differentiation-and-progenitor-pool-expansion-in-the-developing-cortex-by-soxc-genes
#19
Chao Chen, Garrett A Lee, Ariel Pourmorady, Elisabeth Sock, Maria J Donoghue
As the cerebral cortex forms, specialized molecular cascades direct the expansion of progenitor pools, the differentiation of neurons, or the maturation of discrete neuronal subtypes, together ensuring that the correct amounts and classes of neurons are generated. In several neural systems, the SoxC transcriptional regulators, particularly Sox11 and Sox4, have been characterized as functioning exclusively and redundantly in promoting neuronal differentiation. Using the mouse cerebral cortex as a model, Sox11 and Sox4 were examined in the formation of the most complex part of the mammalian brain...
July 22, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25992874/the-longitudinal-transcriptomic-response-of-the-substantia-nigra-to-intrastriatal-6-hydroxydopamine-reveals-significant-upregulation-of-regeneration-associated-genes
#20
Nicholas M Kanaan, Timothy J Collier, Allyson Cole-Strauss, Tessa Grabinski, Zachary R Mattingly, Mary E Winn, Kathy Steece-Collier, Caryl E Sortwell, Fredric P Manfredsson, Jack W Lipton
We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult...
2015: PloS One
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