Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during forebrain and lens development
Open accessAbstract
The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using forebrain and lens chromatin from mice. A total of 3514 (forebrain) and 3723 (lens) Pax6-containing peaks were identified, with ∼70% of them found in both tissues and thereafter called 'common' peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, Pax6-PD/HD and Pax6-HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit via components of FGF (Fgfr2, Prox1 and Ccnd1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Few public ChIP-seq profiles exist for neural-specific transcription factors, and most of those have been performed in the developing mouse neocortex.
“However, very few public chromatin immunoprecipitation sequencing (ChIP-seq) profiles exist, and most of those have been performed in the developing mouse neocortex (Bayam et al., 2015, Notwell et al., 2016, Sun et al., 2015).”
From Multiscale 3D Genome Rewiring during Mouse Neural Development (2017) · cites this paper as Sun et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
MEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648 · see citing works
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
Thorvaldsdottir, H., Robinson, J. T., & Mesirov, J. P. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs017 · Cited by 9,049 · see citing works
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361 · see citing works
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143 · see citing works
Mapping and analysis of chromatin state dynamics in nine human cell types
Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011) · Nature · doi:10.1038/nature09906 · Cited by 2,898 · see citing works
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450 · see citing works
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,238 · see citing works
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233 · see citing works
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia
Landt, S. G., Marinov, G. K., Kundaje, A., Kheradpour, P., Pauli, F., Batzoglou, S., Bernstein, B. E., Bickel, P., Brown, J. B., Cayting, P., et al. (2012) · Genome Research · doi:10.1101/gr.136184.111 · Cited by 2,033 · see citing works
MEME-ChIP: motif analysis of large DNA datasets
Machanick, P., & Bailey, T. L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr189 · Cited by 1,815 · see citing works
Combining evidence using p-values: application to sequence homology searches.
Bailey, T. L., & Gribskov, M. (1998) · Bioinformatics · doi:10.1093/bioinformatics/14.1.48 · Cited by 1,257 · see citing works
NCBI Reference Sequences (RefSeq): current status, new features and genome annotation policy
Pruitt, K. D., Tatusova, T., Brown, G. R., & Maglott, D. R. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr1079 · Cited by 1,149 · cited 2× · see citing works
“Identification of genes with Pax6 binding and data visualization The association of Pax6-peaks to genes was carried out by in-house scripts using the RefSeq (38) annotation, downloaded in February 2013 from the UCSC Genome Browser (39).”
MethodChromatin remodelling during development
Ho, L., & Crabtree, G. R. (2010) · Nature · doi:10.1038/nature08911 · Cited by 1,114 · see citing works
A clustering approach for identification of enriched domains from histone modification ChIP-Seq data
Zang, C., Schones, D. E., Zeng, C., Cui, K., Zhao, K., & Peng, W. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp340 · Cited by 1,043 · see citing works
Identification of novel transcripts in annotated genomes using RNA-Seq
Roberts, A., Pimentel, H., Trapnell, C., & Pachter, L. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr355 · Cited by 963 · see citing works
The UCSC Genome Browser database: extensions and updates 2013
Meyer, L. R., Zweig, A. S., Hinrichs, A. S., Karolchik, D., Kuhn, R. M., Wong, M., Sloan, C. A., Rosenbloom, K. R., Roe, G. R., Rhead, B. L., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1048 · Cited by 901 · see citing works
Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas
St‐Onge, L., Sosa‐Pineda, B., Chowdhury, K., Mansouri, A., & Gruß, P. (1997) · Nature · doi:10.1038/387406a0 · Cited by 792 · see citing works
Glial cells generate neurons: the role of the transcription factor Pax6
Heins, N., Malatesta, P., Cecconi, F., Nakafuku, M., Tucker, K. L., Hack, M. A., Chapouton, P., Barde, Y.-A., & Götz, M. (2002) · Nature Neuroscience · doi:10.1038/nn828 · Cited by 775 · see citing works
Pott, S., & Lieb, J. D. (2014) · Nature Genetics · doi:10.1038/ng.3167 · Cited by 745 · see citing works
Bryne, J. C., Valen, E., Tang, M. E., Marstrand, T. T., Winther, O., da Piedade, I., Krogh, A., Lenhard, B., & Sandelin, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm955 · Cited by 692 · see citing works
Pax6 Controls Radial Glia Differentiation in the Cerebral Cortex
Götz, M., Stoykova, A., & Gruß, P. (1998) · Neuron · doi:10.1016/s0896-6273(00)80621-2 · Cited by 665 · see citing works
Variation in Homeodomain DNA Binding Revealed by High-Resolution Analysis of Sequence Preferences
Berger, M. F., Badis, G., Gehrke, A. R., Talukder, S., Philippakis, A. A., Peña-Castillo, L., Alleyne, T. M., Mnaimneh, S., Botvinnik, O. B., Chan, E. T., et al. (2008) · Cell · doi:10.1016/j.cell.2008.05.024 · Cited by 606 · see citing works
eRNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci
Mousavi, K., Zare, H., Dell’Orso, S., Grøntved, L., Gutierrez-Cruz, G., Derfoul, A., Hager, G. L., & Sartorelli, V. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.07.022 · Cited by 503 · see citing works
Getting your Pax straight: Pax proteins in development and disease
Chi, N., & Epstein, J. A. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(01)02594-x · Cited by 483 · see citing works
Differentiation of mouse embryonic stem cells into a defined neuronal lineage
Bibel, M., Richter, J., Schrenk, K., Tucker, K. L., Staiger, V., Korte, M., Goetz, M., & Barde, Y.-A. (2004) · Nature Neuroscience · doi:10.1038/nn1301 · Cited by 450 · see citing works
An encyclopedia of mouse DNA elements (Mouse ENCODE)
Mouse ENCODE Consortium, Stamatoyannopoulos, J. A., Snyder, M., Hardison, R., Ren, B., Gingeras, T., Gilbert, D. M., Groudine, M., Bender, M., Kaul, R., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-8-418 · Cited by 446 · see citing works
Prox1 function is crucial for mouse lens-fibre elongation
Wigle, J. T., Chowdhury, K., Gruß, P., & Oliver, G. C. (1999) · Nature Genetics · doi:10.1038/6844 · Cited by 432 · see citing works
seqMINER: an integrated ChIP-seq data interpretation platform
Ye, T., Krebs, A. R., Choukrallah, M.-A., Keime, C., Plewniak, F., Davidson, I., & Tora, L. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1287 · Cited by 410 · see citing works
MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets
Shao, Z., Zhang, Y., Yuan, G., Orkin, S. H., & Waxman, D. J. (2012) · Genome biology · doi:10.1186/gb-2012-13-3-r16 · Cited by 402 · see citing works
Sansom, S. N., Griffiths, D. S., Faedo, A., Kleinjan, D., Ruan, Y., Smith, J. C., van Heyningen, V., Rubenstein, J. L. R., & Livesey, F. J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000511 · Cited by 401 · see citing works
Castro, D. S., Martynoga, B., Parras, C. M., Ramesh, V., Pacary, E., Johnston, C., Drechsel, D., Lebel, M., Garcia, L. G., Hunt, C., et al. (2011) · Genes & Development · doi:10.1101/gad.627811 · Cited by 396 · see citing works
Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2
Toresson, H., Potter, S. S., & Campbell, K. (2000) · Development · doi:10.1242/dev.127.20.4361 · Cited by 387 · see citing works
Epstein, J. A., Cai, J., Glaser, T. M., Jepeal, L. I., & Maas, R. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37201-0 · Cited by 368 · see citing works
Epstein, J. A., Glaser, T. M., Cai, J., Jepeal, L. I., Walton, D. S., & Maas, R. L. (1994) · Genes & Development · doi:10.1101/gad.8.17.2022 · Cited by 362 · see citing works
Generating neuronal diversity in the retina: one for nearly all
Marquardt, T., & Gruß, P. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02028-2 · Cited by 361 · see citing works
Xu, H. E., Rould, M. A., Xu, W., Epstein, J. A., Maas, R. L., & Pabo, C. O. (1999) · Genes & Development · doi:10.1101/gad.13.10.1263 · Cited by 311 · see citing works
Czerny, T., & Busslinger, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.5.2858 · Cited by 297 · see citing works
Distinctcis-Essential Modules Direct the Time–Space Pattern of thePax6Gene Activity
Kammandel, B., Chowdhury, K., Stoykova, A., Aparicio, S. A. J. R., Brenner, S., & Gruß, P. (1999) · Developmental Biology · doi:10.1006/dbio.1998.9128 · Cited by 279 · see citing works
Direct and concentration-dependent regulation of the proneural gene Neurogenin2 by Pax6
Scardigli, R., Bäumer, N., Gruss, P., Guillemot, F., & Roux, I. L. (2003) · Development · doi:10.1242/dev.00539 · Cited by 239 · see citing works
The cellular and molecular mechanisms of vertebrate lens development
Cvekl, A., & Ashery-Padan, R. (2014) · Development · doi:10.1242/dev.107953 · Cited by 227 · see citing works
Self-citationQuinn, J. C., Molinek, M., Martynoga, B., Zaki, P. A., Faedo, A., Bulfone, A., Hevner, R. F., West, J. D., & Price, D. J. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.035 · Cited by 223 · see citing works
The genetic and molecular basis of congenital eye defects
Graw, J. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1202 · Cited by 214 · see citing works
Pax genes: regulators of lineage specification and progenitor cell maintenance
Blake, J. A., & Ziman, M. R. (2014) · Development · doi:10.1242/dev.091785 · Cited by 214 · see citing works
Cooperative interactions between paired domain and homeodomain
Jun, S., & Desplan, C. (1996) · Development · doi:10.1242/dev.122.9.2639 · Cited by 212 · see citing works
Comparative Epigenomic Annotation of Regulatory DNA
Shu Dong, X. I. A. O., Xie, D., Cao, X., Yu, P., Xing, X., Chen, C.-C., Musselman, M., Xie, M., West, F. D., Lewin, H. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.029 · Cited by 199 · see citing works
Soleimani, V. D., Punch, V. G., Kawabe, Y.-I., Jones, A., Palidwor, G., Porter, C. J., Cross, J. W., Carvajal, J. J., Kockx, C. E. M., van IJcken, W. F. J., et al. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.03.014 · Cited by 192 · see citing works
Molecular Control of Neurogenesis: A View from the Mammalian Cerebral CortexPreprint
Martynoga, B., Drechsel, D., & Guillemot, F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008359 · Cited by 187 · see citing works
The role of Pax6 in forebrain development
Georgala, P. A., Carr, C. B., & Price, D. J. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20895 · Cited by 183 · see citing works
Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation
Zhao, H., Yang, T., Madakashira, B. P., Thiels, C. A., Bechtle, C. A., Garcia, C. M., Zhang, H., Yu, K., Ornitz, D. M., Beebe, D. C., et al. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.03.028 · Cited by 171 · see citing works
Srinivasan, K., Leone, D. P., Bateson, R. K., Dobreva, G., Kohwi, Y., Kohwi-Shigematsu, T., Grosschedl, R., & McConnell, S. K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216793109 · Cited by 171 · see citing works
Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development
Kioussi, C., O’Connell, S. M., St‐Onge, L., Treier, M., Gleiberman, A. S., Gruß, P., & Rosenfeld, M. G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14378 · Cited by 159 · see citing works
FoxP2 Regulates Neurogenesis during Embryonic Cortical Development
Tsui, D. C. C., Vessey, J. P., Tomita, H., Kaplan, D. R., & Miller, F. D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-12.2013 · Cited by 151 · see citing works
Duncan, M. K., Kozmík, Z., Cveklová, K., et al. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.18.3173 · Cited by 148 · see citing works
A highly conserved lens transcriptional control element from the Pax-6 gene
Williams, S., Altmann, C. R., Chow, R. L., Hemmati‐Brivanlou, A., & Lang, R. A. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00057-4 · Cited by 143 · see citing works
Ocular surface epithelial and stem cell development
Wolosin, J. M., Budak, M. T., & Akinci, M. A. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041876jw · Cited by 131 · see citing works
Pax6 is essential for lens fiber cell differentiation
Shaham, O., Smith, A. N., Robinson, M. L., et al. (2009) · Development · doi:10.1242/dev.032888 · Cited by 127 · see citing works
Notch signaling regulates growth and differentiation in the mammalian lens
Rowan, S., Conley, K. W., Le, T. T., et al. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.06.002 · Cited by 125 · see citing works
Dosage requirement and allelic expression of PAX6 during lens placode formation
Raamsdonk, C. D. V., & Tilghman, S. M. (2000) · Development · doi:10.1242/dev.127.24.5439 · Cited by 123 · see citing works
Sox2 and Pou2f1 interact to control lens and olfactory placode development
Donner, A. L., Episkopou, V., & Maas, R. L. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.10.047 · Cited by 122 · see citing works
Pax-6 and Cdx-2/3 Interact to Activate Glucagon Gene Expression on the G1 Control Element
Ritz-Laser, B., Estreicher, A., Klages, N., Saule, S., & Philippé, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.7.4124 · Cited by 117 · see citing works
Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon
Holm, P. C., Mader, M. T., Haubst, N., Wizenmann, A., Sigvardsson, M., & Götz, M. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.10.008 · Cited by 117 · see citing works
Precocious retinal neurons: Pax6 controls timing of differentiation and determination of cell type
Philips, G. T., Stair, C. N., Lee, H. Y., Wroblewski, E. E., Berberoglu, M. A., Brown, N. L., & Mastick, G. S. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.12.018 · Cited by 112 · see citing works
Pax6 Regulates Gene Expression in the Vertebrate Lens through miR-204
Shaham, O., Gueta, K., Mor, E., Oren‐Giladi, P., Grinberg, D., Xie, Q. M., Cvekl, A., Shomron, N., Davis, N., Keydar-Prizant, M., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003357 · Cited by 107 · see citing works
Self-citationRegulation of αA‐crystallin via Pax6, c‐Maf, CREB and a broad domain of lens‐specific chromatin
Yang, Y., Stopka, T., Golestaneh, N., Wang, Y., Wu, K., Li, A., Chauhan, B. K., Gao, C., Cveklová, K., Duncan, M. K., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601114 · Cited by 107 · see citing works
Self-citationGenome-wide identification of direct targets of the Drosophila retinal determination protein EyelessPreprint
Ostrin, E. J., Li, Y., Hoffman, K. L., Liu, J., Wang, K., Zhang, L., Mardon, G., & Chen, R. (2006) · Genome Research · doi:10.1101/gr.4673006 · Cited by 105 · see citing works
The upstream ectoderm enhancer inPax6has an important role in lens induction
Dimanlig, P. V., Faber, S. C., Auerbach, W., et al. (2001) · Development · doi:10.1242/dev.128.22.4415 · Cited by 102 · see citing works
Topark‐Ngarm, A., Golonzhka, O., Peterson, V. J., Barrett, B., Martinez, B., Crofoot, K., Filtz, T. M., & Leid, M. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602776200 · Cited by 97 · see citing works
Mafs, Prox1, and Pax6 Can Regulate Chicken βB1-Crystallin Gene Expression
Cui, W., Tomarev, S. I., Piatigorsky, J., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312414200 · Cited by 92 · see citing works
The mechanism of lens placode formation: A case of matrix-mediated morphogenesis
Huang, J., Rajagopal, R., Liu, Y., et al. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.04.008 · Cited by 91 · see citing works
Raviv, S., Bharti, K., Rencus‐Lazar, S., Cohen‐Tayar, Y., Schyr, R. B., Evantal, N., Meshorer, E., Zilberberg, A., Idelson, M., Reubinoff, B. E., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004360 · Cited by 88 · see citing works
Self-citationCell-autonomous involvement ofMab21l1is essential for lens placode development
Yamada, R., Mizutani-Koseki, Y., Hasegawa, T., et al. (2003) · Development · doi:10.1242/dev.00399 · Cited by 88 · see citing works
Jia, J., Lin, M., Zhang, L., York, J. P., & Zhang, P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00780-07 · Cited by 82 · see citing works
Mi, D., Carr, C. B., Georgala, P. A., Huang, Y.-T., Manuel, M. N., Jeanes, E. C., Niisato, E., Sansom, S. N., Livesey, F. J., Theil, T., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.012 · Cited by 78 · see citing works
Epigenetic regulatory mechanisms in vertebrate eye development and disease
Cvekl, A., & Mitton, K. P. (2010) · Heredity · doi:10.1038/hdy.2010.16 · Cited by 77 · see citing works
Self-citationXie, Q. M., Yang, Y., Huang, J., Ninkovic, J., Walcher, T., Wolf, L. V., Vitenzon, A., Zheng, D., Götz, M., Beebe, D. C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054507 · Cited by 76 · see citing works
Self-citationPax6 dosage requirements in iris and ciliary body differentiation
Davis, N., Yoffe, C., Raviv, S., et al. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.06.023 · Cited by 75 · see citing works
Walcher, T., Xie, Q. M., Sun, J., Irmler, M., Beckers, J., Öztürk, T., Niessing, D., Stoykova, A., Cvekl, A., Ninkovic, J., et al. (2013) · Development · doi:10.1242/dev.082875 · Cited by 72 · see citing works
Self-citationChauhan, B. K. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh334 · Cited by 67 · see citing works
Blixt, Å., Landgren, H., Johansson, B. R., et al. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.09.021 · Cited by 67 · see citing works
Wolf, L. V., Harrison, W. R., Huang, J., Xie, Q. M., Xiao, N., Sun, J., Kong, L., Lachke, S. A., Kuracha, M. R., Govindarajan, V., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt824 · Cited by 63 · see citing works
Self-citationYang, Y., & Cvekl, A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.05.072 · Cited by 62 · see citing works
Self-citationThe Orchestration of Mammalian Tissue Morphogenesis through a Series of Coherent Feed-forward Loops
Xie, Q. M., & Cvekl, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.264580 · Cited by 61 · see citing works
Self-citationDmrta1 regulates proneural gene expression downstream of P ax6 in the mammalian telencephalon
Kikkawa, T., Obayashi, T., Takahashi, M., et al. (2013) · Genes to Cells · doi:10.1111/gtc.12061 · Cited by 58 · see citing works
Sugiyama, Y., Stump, R. J. W., Nguyen, A., Li, W., Chen, Y., Wang, Y., Murdoch, J. N., Lovicu, F. J., & McAvoy, J. W. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.11.033 · Cited by 57 · see citing works
Discovery and assessment of conserved Pax6 target genes and enhancersPreprint
Coutinho, P., Pavlou, S., Bhatia, S., Chalmers, K. J., Kleinjan, D. A., & van Heyningen, V. (2011) · Genome Research · doi:10.1101/gr.124115.111 · Cited by 57 · see citing works
Nikoletopoulou, V., Plachta, N., Allen, N. D., Pinto, L., Götz, M., & Barde, Y. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.08.011 · Cited by 54 · see citing works
Canto-Soler, M. V., & Adler, R. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.02.033 · Cited by 51 · see citing works
Pitx3 controls multiple aspects of lens development
Medina-Martínez, O., Shah, R., & Jamrich, M. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21924 · Cited by 49 · see citing works
Cocas, L. A., Georgala, P. A., Mangin, J., Clegg, J. M., Kessaris, N., Haydar, T. F., Gallo, V., Price, D. J., & Corbin, J. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3867-10.2011 · Cited by 48 · see citing works
Transcription factor GATA‐3 is essential for lens development
Maeda, A., Moriguchi, T., Hamada, M., et al. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22035 · Cited by 48 · see citing works
A balance of FGF and BMP signals regulates cell cycle exit andEquarinexpression in lens cells
Jarrı́n, M., Pandit, T., & Gunhaga, L. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-01-0075 · Cited by 43 · see citing works
Hmga2 regulates self-renewal of retinal progenitors
Parameswaran, S., Xia, X., Hegde, G., & Ahmad, I. (2014) · Development · doi:10.1242/dev.107326 · Cited by 40 · see citing works
Weinandy, F., Ninkovic, J., & Götz, M. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07602.x · Cited by 40 · see citing works
Pax6-dependent, but β-catenin-independent, function of Bcl9 proteins in mouse lens developmentPreprint
Cantù, C., Zimmerli, D., Hausmann, G., Valenta, T., Moor, A. E., Aguet, M., & Basler, K. (2014) · Genes & Development · doi:10.1101/gad.246140.114 · Cited by 37 · see citing works
Er81is a downstream target of Pax6 in cortical progenitors
Tuoc, T., & Stoykova, A. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-23 · Cited by 35 · see citing works
Chauhan, B. K., Plageman, T. F., Lou, M., & Lang, R. A. (2015) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2014.11.011 · Cited by 29 · see citing works
Zuccotti, A., Magueresse, C. L., Chen, M., Neitz, A., & Monyer, H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320290111 · Cited by 27 · see citing works
The Wasp System: An open source environment for managing and analyzing genomic data
McLellan, A. S., Dubin, R. A., Jing, Q., et al. (2012) · Genomics · doi:10.1016/j.ygeno.2012.08.005 · Cited by 23 · see citing works
Dual Roles for Prox1 in the Regulation of the Chicken βB1-Crystallin Promoter
Chen, X., Taube, J. R., Simirskii, V. N., Patel, T. P., & Duncan, M. K. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-1300 · Cited by 22 · see citing works
Xie, Q. M., Ung, D. C., Хафизов, К. Ф., Fiser, A., & Cvekl, A. (2014) · Europe PMC (PubMed Central) · Cited by 22 · see citing works
Self-citationForsdahl, S., Kiselev, Y., Hogseth, R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102559 · Cited by 17 · see citing works
Yeo, G. W.-M., Coufal, N. G., Aigner, S., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn065 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Multiscale 3D Genome Rewiring during Mouse Neural Development
Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.-P., Tanay, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.043 · Cited by 1,338 · see citing works
- Authors
- Sun, J., Rockowitz, S., Xie, Q., Ashery-Padan, R., Zheng, D., & Cvekl, A.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-07-02
- Volume
- 43
- Issue
- 14
- Pages
- 6827-6846
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4538810
- OpenAlex
- W2105720738
- Cited by
- 113
- References
- 106
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 19 · 2017: 8 · 2016: 6 · 2015: 4
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- Yeshiva University
- National Institutes of Health
- Albert Einstein College of Medicine, Yeshiva University
- National Institute of Mental Health (R21MH099452)
- National Eye Institute (R01EY012200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- Pax6, DNA binding mechanism, gene regulatory networks, forebrain development, lens development, transcription factor binding sites, enhancers, H3K4me1, H3K4me3, H3K27ac, H3K27me3, RNA polymerase II, cortical neurogenesis, cell cycle exit, FGF signaling, Wnt signaling, Ngn2, ASCL1, Fezf2, Gsx2, Prox1, FGFR2, DKK3, Wnt7a, LRP6, BCL9L, CCND1, organogenesis
- MeSH terms
- PAX6 Transcription Factor, Animals, Binding Sites, Chromatin, DNA, Enhancer Elements, Genetic, Eye Proteins, Lens, Crystalline, Protein Binding, Repressor Proteins, Transcription, Genetic, Prosencephalon, Mice, Knockout, Homeodomain Proteins, Gene Expression Regulation, Developmental, Mice, Paired Box Transcription Factors, Gene Regulatory Networks, Neurogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
