Search

Your search keyword '"Martynoga, Ben"' showing total 42 results
Start Over Author "Martynoga, Ben"
42 results on '"Martynoga, Ben"'

2. Foxg1 : a pleiotropic regulator of telencephalic development

Author

Martynoga, Ben

Subjects
611
Abstract

This thesis focuses on the role of the forkhead box factor Foxg1 in the development of the vertebrate telencephalon. Mice mutant for Foxg1 exhibit multiple telencephalic defects demonstrative of an important pleiotropic role of rFoxg1 in telencephalic organogenesis. Severe hypoplasia of the null mutant telencephalon demonstrates that Foxg1 is required for the regulation of telencephalic growth. Experiments descried in this thesis provide the most systematic study to date of the mechanisms by which Foxg1 regulates this process. Broadly, the results demonstrate that Foxg1 is required to maintain progenitor cell fate, at the expense of differentiated cell fate, and to maintain the proliferation rate of progenitors. In addition to telencephalic growth defects, it has been documented that ventral telencephalic cell fates are lost in Foxg1-/- embryos. This thesis demonstrates that all ventral telencephalic lineages, which give rise to the basal ganglia and neuronal and glial constituents of the cerebral cortex, are completely absent in Foxg1-/- embryos. The requirement for Foxg1 to repress ectopic dorsal genes and to activate ventral genes is consistent with a role in regulating the response to ventralising signals. The hypothesis that Foxg1 is required for telencephalic cells to respond appropriately to the ventralising morphogen Shh is advanced. Evidence is provided for a role of Foxg1 in the regulation of the expression and activity of Gli3, the major antagonist of the hedgehog signalling pathway. In Foxg1-/-; Gli3-/- telencephalon, some aspects of ventral telencephalic fate are recovered. This demonstrates that Foxg1 is required for ventral fate specification, in part through the antagonism of Gli3 action, consistent with the original hypothesis. However, markers of ventro-medial telencephalic fate are not recovered and ectopic expression of dorsal markers persists in double mutants. From these findings it is argued that Foxg1 has hedgehog-independent roles in dorso-ventral patterning of the telencephalon.

Published
2007

11. Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis

Author

Martynoga, Ben, Morrison, Harris, Price, David J., and Mason, John O.

Subjects
Immunohistochemistry, Apoptosis, Fibroblast growth factors, Cell research, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.04.005 Byline: Ben Martynoga (a), Harris Morrison (b), David J. Price (a), John O. Mason (a) Abstract: Null mutation of the Foxg1 gene causes hypoplasia of the mouse telencephalon and loss of ventral telencephalic structures. We show that a crucial early requirement for Foxg1 is in the induction of ventral cell fate in the telencephalon. To study later proliferative defects, we have adapted an iododeoxyuridine and bromodeoxyuridine double labeling protocol for use in the developing embryo, which allows estimation of cell cycle kinetics in a single specimen. This technique is used to demonstrate that the cell cycle is prematurely lengthened in the Foxg1-null telencephalon. These defects are first apparent at embryonic day 10.5 (E10.5) and are most severe in the rostral telencephalon. We show that apoptosis is also reduced in the same rostral domain. These defects correspond temporally and spatially with a dramatic reduction in expression of the potent signaling molecule Fgf8. We also show that in the absence of Foxg1 an excess of neurons is produced from E11.5, depleting the progenitor pool and limiting the growth of the Foxg1.sup.-/- telencephalon. The increase in neurogenic division coincides with an increase in BMP signaling, as detected by immunohistochemistry for phosphorylated smad-1, -5, and -8. This study reinforces Foxg1's position as a major regulator of telencephalic neurogenesis and supports the idea that Foxg1 controls precursor proliferation via regulation of Fgf signaling and differentiation via regulation of Bmp signaling. Author Affiliation: (a) Genes and Development Group, Biomedical Sciences, George Square, The University of Edinburgh, Edinburgh EH8 9XD, UK (b) MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Published
2005

13. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance

Author

Bertolini, J, Favaro, R, Zhu, Y, Pagin, M, Ngan, C, Wong, C, Tjong, H, Vermunt, M, Martynoga, B, Barone, C, Mariani, J, Cardozo, M, Tabanera, N, Zambelli, F, Mercurio, S, Ottolenghi, S, Robson, P, Creyghton, M, Bovolenta, P, Pavesi, G, Guillemot, F, Nicolis, S, Wei, C, Bertolini, Jessica A., Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W., Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P., Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K., Wei, Chia-Lin, Bertolini, J, Favaro, R, Zhu, Y, Pagin, M, Ngan, C, Wong, C, Tjong, H, Vermunt, M, Martynoga, B, Barone, C, Mariani, J, Cardozo, M, Tabanera, N, Zambelli, F, Mercurio, S, Ottolenghi, S, Robson, P, Creyghton, M, Bovolenta, P, Pavesi, G, Guillemot, F, Nicolis, S, Wei, C, Bertolini, Jessica A., Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W., Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P., Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K., and Wei, Chia-Lin

Abstract

The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders

Published
2019

14. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance

Author

Bertolini, Jessica A, Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W, Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P, Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K, Wei, Chia-Lin, Bertolini, Jessica A, Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W, Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P, Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K, and Wei, Chia-Lin

Abstract

The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders.

Published
2019

15. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance

Author

Hubrecht Institute with UMC, Bertolini, Jessica A., Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W., Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P., Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K., Wei, Chia Lin, Hubrecht Institute with UMC, Bertolini, Jessica A., Favaro, Rebecca, Zhu, Yanfen, Pagin, Miriam, Ngan, Chew Yee, Wong, Chee Hong, Tjong, Harianto, Vermunt, Marit W., Martynoga, Ben, Barone, Cristiana, Mariani, Jessica, Cardozo, Marcos Julián, Tabanera, Noemi, Zambelli, Federico, Mercurio, Sara, Ottolenghi, Sergio, Robson, Paul, Creyghton, Menno P., Bovolenta, Paola, Pavesi, Giulio, Guillemot, Francois, Nicolis, Silvia K., and Wei, Chia Lin

Published
2019

16. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance

Author

Bertolini, Jessica A., primary, Favaro, Rebecca, additional, Zhu, Yanfen, additional, Pagin, Miriam, additional, Ngan, Chew Yee, additional, Wong, Chee Hong, additional, Tjong, Harianto, additional, Vermunt, Marit W., additional, Martynoga, Ben, additional, Barone, Cristiana, additional, Mariani, Jessica, additional, Cardozo, Marcos Julián, additional, Tabanera, Noemi, additional, Zambelli, Federico, additional, Mercurio, Sara, additional, Ottolenghi, Sergio, additional, Robson, Paul, additional, Creyghton, Menno P., additional, Bovolenta, Paola, additional, Pavesi, Giulio, additional, Guillemot, Francois, additional, Nicolis, Silvia K., additional, and Wei, Chia-Lin, additional

Published
2019
Full Text
View/download PDF

17. The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels

Author

Quinn Jane C, Molinek Mike D, Martynoga Ben, Manuel Martine N, Kroemmer Corinne, Mason John O, and Price David J

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of Foxg1 null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed Foxg1+/+↔Foxg1-/- chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells. Results Our analysis showed that the Foxg1-/- cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in Foxg1-/- dorsal telencephalic cells. We went on to show that the introduction into Foxg1-/- embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects. Conclusions We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner.

Published
2011
Full Text
View/download PDF

18. Corrigendum: Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

Author

Mateo, Juan L., primary, van den Berg, Debbie L.C., additional, Haeussler, Maximilian, additional, Drechsel, Daniela, additional, Gaber, Zachary B., additional, Castro, Diogo S., additional, Robson, Paul, additional, Lu, Q. Richard, additional, Crawford, Gregory E., additional, Flicek, Paul, additional, Ettwiller, Laurence, additional, Wittbrodt, Joachim, additional, Guillemot, François, additional, and Martynoga, Ben, additional

Published
2017
Full Text
View/download PDF

20. Corrigendum: Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

Author

Mateo, Juan L., primary, van den Berg, Debbie L.C., additional, Haeussler, Maximilian, additional, Drechsel, Daniela, additional, Gaber, Zachary B., additional, Castro, Diogo S., additional, Robson, Paul, additional, Lu, Q. Richard, additional, Crawford, Gregory E., additional, Flicek, Paul, additional, Ettwiller, Laurence, additional, Wittbrodt, Joachim, additional, Guillemot, François, additional, and Martynoga, Ben, additional

Published
2016
Full Text
View/download PDF

21. NFIX regulates proliferation and migration within the murine SVZ neurogenic niche

Author

Heng, Evelyn, Zhou, Bo, Harris, Lachlan, Harvey, Tracey, Smith, Aaron, Horne, Elise, Martynoga, Ben, Andersen, Jimena, Achimastou, Angeliki, Cato, Kathleen, Richards, Linda, Gronostajski, Richard, Yeo, Giles, Guillemot, Francois, Bailey, Timothy, Piper, Michael, Heng, Evelyn, Zhou, Bo, Harris, Lachlan, Harvey, Tracey, Smith, Aaron, Horne, Elise, Martynoga, Ben, Andersen, Jimena, Achimastou, Angeliki, Cato, Kathleen, Richards, Linda, Gronostajski, Richard, Yeo, Giles, Guillemot, Francois, Bailey, Timothy, and Piper, Michael

Abstract

Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix(-/-) mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix(-/-) mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix(-/-) mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix(-/-) mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.

Published
2015

24. NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche

Author

Heng, Yee Hsieh Evelyn, primary, Zhou, Bo, additional, Harris, Lachlan, additional, Harvey, Tracey, additional, Smith, Aaron, additional, Horne, Elise, additional, Martynoga, Ben, additional, Andersen, Jimena, additional, Achimastou, Angeliki, additional, Cato, Kathleen, additional, Richards, Linda J., additional, Gronostajski, Richard M., additional, Yeo, Giles S., additional, Guillemot, François, additional, Bailey, Timothy L., additional, and Piper, Michael, additional

Published
2014
Full Text
View/download PDF

25. Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

Author

Mateo, Juan L., primary, van den Berg, Debbie L.C., additional, Haeussler, Maximilian, additional, Drechsel, Daniela, additional, Gaber, Zachary B., additional, Castro, Diogo S., additional, Robson, Paul, additional, Lu, Q. Richard, additional, Crawford, Gregory E., additional, Flicek, Paul, additional, Ettwiller, Laurence, additional, Wittbrodt, Joachim, additional, Guillemot, François, additional, and Martynoga, Ben, additional

Published
2014
Full Text
View/download PDF

26. A Transcriptional Mechanism Integrating Inputs from Extracellular Signals to Activate Hippocampal Stem Cells

Author

Andersen, Jimena, primary, Urbán, Noelia, additional, Achimastou, Angeliki, additional, Ito, Ayako, additional, Simic, Milesa, additional, Ullom, Kristy, additional, Martynoga, Ben, additional, Lebel, Mélanie, additional, Göritz, Christian, additional, Frisén, Jonas, additional, Nakafuku, Masato, additional, and Guillemot, François, additional

Published
2014
Full Text
View/download PDF

27. Hierarchical Mechanisms for Direct Reprogramming of Fibroblasts to Neurons

Author

Wapinski, Orly L., primary, Vierbuchen, Thomas, additional, Qu, Kun, additional, Lee, Qian Yi, additional, Chanda, Soham, additional, Fuentes, Daniel R., additional, Giresi, Paul G., additional, Ng, Yi Han, additional, Marro, Samuele, additional, Neff, Norma F., additional, Drechsel, Daniela, additional, Martynoga, Ben, additional, Castro, Diogo S., additional, Webb, Ashley E., additional, Südhof, Thomas C., additional, Brunet, Anne, additional, Guillemot, Francois, additional, Chang, Howard Y., additional, and Wernig, Marius, additional

Published
2013
Full Text
View/download PDF

28. Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

Author

Martynoga, Ben, primary, Mateo, Juan L., additional, Zhou, Bo, additional, Andersen, Jimena, additional, Achimastou, Angeliki, additional, Urbán, Noelia, additional, van den Berg, Debbie, additional, Georgopoulou, Dimitra, additional, Hadjur, Suzana, additional, Wittbrodt, Joachim, additional, Ettwiller, Laurence, additional, Piper, Michael, additional, Gronostajski, Richard M., additional, and Guillemot, François, additional

Published
2013
Full Text
View/download PDF

29. FOXO3 Shares Common Targets with ASCL1 Genome-wide and Inhibits ASCL1-Dependent Neurogenesis

Author

Webb, Ashley E., primary, Pollina, Elizabeth A., additional, Vierbuchen, Thomas, additional, Urbán, Noelia, additional, Ucar, Duygu, additional, Leeman, Dena S., additional, Martynoga, Ben, additional, Sewak, Madhavi, additional, Rando, Thomas A., additional, Guillemot, François, additional, Wernig, Marius, additional, and Brunet, Anne, additional

Published
2013
Full Text
View/download PDF

32. A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Author

Castro, Diogo S., primary, Martynoga, Ben, additional, Parras, Carlos, additional, Ramesh, Vidya, additional, Pacary, Emilie, additional, Johnston, Caroline, additional, Drechsel, Daniela, additional, Lebel-Potter, Mélanie, additional, Garcia, Laura Galinanes, additional, Hunt, Charles, additional, Dolle, Dirk, additional, Bithell, Angela, additional, Ettwiller, Laurence, additional, Buckley, Noel, additional, and Guillemot, François, additional

Published
2011
Full Text
View/download PDF

34. Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments

Author

Onorati, Marco, primary, Binetti, Maurizio, additional, Conti, Luciano, additional, Camnasio, Stefano, additional, Calabrese, Giovanna, additional, Albieri, Ilaria, additional, Di Febo, Francesca, additional, Toselli, Mauro, additional, Biella, Gerardo, additional, Martynoga, Ben, additional, Guillemot, Francois, additional, Consalez, G. Giacomo, additional, and Cattaneo, Elena, additional

Published
2010
Full Text
View/download PDF

37. Controlled overexpression of Pax6 in vivo negatively autoregulates thePax6locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization

Author

Manuel, Martine, primary, Georgala, Petrina A., additional, Carr, Catherine B., additional, Chanas, Simon, additional, Kleinjan, Dirk A., additional, Martynoga, Ben, additional, Mason, John O., additional, Molinek, Michael, additional, Pinson, Jeni, additional, Pratt, Thomas, additional, Quinn, Jane C., additional, Simpson, T. Ian, additional, Tyas, David A., additional, van Heyningen, Veronica, additional, West, John D., additional, and Price, David J., additional

Published
2007
Full Text
View/download PDF

38. Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

Author

Mateo, Juan L., van den Berg, Debbie L.C., Haeussler, Maximilian, Drechsel, Daniela, Gaber, Zachary B., Castro, Diogo S., Robson, Paul, Crawford, Gregory E., Flicek, Paul, Ettwiller, Laurence, Wittbrodt, Joachim, Guillemot, Francois, and Martynoga, Ben

Abstract

The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.

Published
2015
Full Text
View/download PDF

39. Chill out.

Author

Martynoga, Ben

Subjects
*PHYSIOLOGICAL stress, *STRESS management, *TRANQUILIZING drugs
Abstract

The article offers information on research on stress. Particular focus is given to how stress might not be as destructive to health as was previously assumed. Additional topics discussed include the use of anti-anxiety drugs such as Xanax and Ativan in the U.S., the possibility that stress is addictive and insights on the benefits of prosocial behavior from Paul Piff, a social psychologist at the University of California, Irvine.

Published
2016

41. Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization.

Author

Manuel, Martine, Georgala, Petrina A., Carr, Catherine B., Chanas, Simon, Kleinjan, Dirk A., Martynoga, Ben, Mason, John O., Molinek, Michael, Pinson, Jeni, Pratt, Thomas, Quinn, Jane C., Simpson, T. Ian, Tyas, David A., Van Heyningen, Veronica, West, John D., and Price, David J.

Subjects
TRANSCRIPTION factors, PROTEINS, GENE expression, GENETIC regulation, TRANSGENIC mice
Abstract

Levels of expression of the transcription factor Pax6 vary throughout corticogenesis in a rostro-lateralhigh to caudo-mediallow gradient across the cortical proliferative zone. Previous loss-of-function studies have indicated that Pax6 is required for normal cortical progenitor proliferation, neuronal differentiation, cortical lamination and cortical arealization, but whether and how its level of expression affects its function is unclear. We studied the developing cortex of PAX77 YAC transgenic mice carrying several copies of the human PAX6 locus with its full complement of regulatory regions. We found that PAX77 embryos express Pax6 in a normal spatial pattern, with levels up to three times higher than wild type. By crossing PAX77 mice with a new YAC transgenic line that reports Pax6 expression (DTy54), we showed that increased expression is limited by negative autoregulation. Increased expression reduces proliferation of late cortical progenitors specifically, and analysis of PAX77 ↔wild-type chimeras indicates that the defect is cell autonomous. We analyzed cortical arealization in PAX77 mice and found that, whereas the loss of Pax6 shifts caudal cortical areas rostrally, Pax6 overexpression at levels predicted to shift rostral areas caudally has very little effect. These findings indicate that Pax6 levels are stabilized by autoregulation, that the proliferation of cortical progenitors is sensitive to altered Pax6 levels and that cortical arealization is not. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

42. Molecular control of neurogenesis: a view from the mammalian cerebral cortex.

Author

Martynoga B, Drechsel D, and Guillemot F

Subjects
Animals, Cell Differentiation genetics, Cerebral Cortex embryology, Cerebral Cortex metabolism, Gene Expression Regulation, Developmental, Mammals genetics, Mammals metabolism, Models, Biological, Neural Plate embryology, Neural Plate metabolism, Neural Plate physiology, Neurogenesis genetics, Cerebral Cortex growth & development, Epigenesis, Genetic, Mammals growth & development, Neurogenesis physiology, Signal Transduction
Abstract

The mammalian nervous system is the most complex organ of any living organism. How this complexity is generated during neural development is just beginning to be elucidated. This article discusses the signaling, transcriptional, and epigenetic mechanisms that are involved in neural development. The first part focuses on molecules that control neuronal numbers through regulation of the timing of onset of neurogenesis, the timing of the neuronal-to-glial switch, and the rate of progenitor proliferation. The second part focuses on molecules that control neuronal diversity by generating spatially or temporally distinct populations of neuronal progenitors. Most of the studies discussed in this article are focused on the developing mammalian cerebral cortex, because this is one of the main model systems for neural developmental studies and many of the mechanisms identified in this tissue also operate elsewhere in the developing brain and spinal cord.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results