{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:56:52Z","timestamp":1791421012913,"version":"4.3.3"},"reference-count":56,"publisher":"The Company of Biologists","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:p>The developing central nervous system is partitioned into compartments by boundary cells, which have different properties than compartment cells, such as forming neuron-free zones, proliferating more slowly and acting as organizing centers. We now report that in mice the bHLH factor Hes1 is persistently expressed at high levels by boundary cells but at variable levels by non-boundary cells. Expression levels of Hes1 display an inverse correlation to those of the proneural bHLH factor Mash1, suggesting that downregulation of Hes1 leads to upregulation of Mash1 in non-boundary regions,whereas persistent and high Hes1 expression constitutively represses Mash1 in boundary regions. In agreement with this notion, in the absence of Hes1 and its related genes Hes3 and Hes5, proneural bHLH genes are ectopically expressed in boundaries, resulting in ectopic neurogenesis and disruption of the organizing centers. Conversely, persistent Hes1 expression in neural progenitors prepared from compartment regions blocks neurogenesis and reduces cell proliferation rates. These results indicate that the mode of Hes1 expression is different between boundary and non-boundary cells, and that persistent and high levels of Hes1 expression constitutively repress proneural bHLH gene expression and reduce cell proliferation rates,thereby forming boundaries that act as the organizing centers.<\/jats:p>","DOI":"10.1242\/dev.02403","type":"journal-article","created":{"date-parts":[[2006,5,26]],"date-time":"2006-05-26T00:37:19Z","timestamp":1148603839000},"page":"2467-2476","source":"Crossref","is-referenced-by-count":212,"title":["Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system"],"prefix":"10.1242","volume":"133","author":[{"given":"Joung Hee","family":"Baek","sequence":"first","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Shogoin-Kawahara,Sakyo-ku, Kyoto 606-8507, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Shogoin-Kawahara,Sakyo-ku, Kyoto 606-8507, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Shogoin-Kawahara,Sakyo-ku, Kyoto 606-8507, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ohtsuka","sequence":"additional","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Shogoin-Kawahara,Sakyo-ku, Kyoto 606-8507, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichiro","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Institute for Virus Research, Kyoto University, Shogoin-Kawahara,Sakyo-ku, Kyoto 606-8507, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042612032339000_REF1","doi-asserted-by":"crossref","unstructured":"Akazawa, C., Ishibashi, M., Shimizu, C., Nakanishi, S. and Kageyama, R. (1995). A mammalian helix-loop-helix factor structurally related to the product of Drosophila proneural gene atonal is a positive transcriptional regulator expressed in the developing nervous system. J. Biol. Chem.270,8730-8738.","DOI":"10.1074\/jbc.270.15.8730"},{"key":"2021042612032339000_REF2","doi-asserted-by":"crossref","unstructured":"Braun, M. M., Etheridge, A., Bernard, A., Robertson, C. P. and Roelink, H. (2003). Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain. Development130,5579-5587.","DOI":"10.1242\/dev.00685"},{"key":"2021042612032339000_REF3","doi-asserted-by":"crossref","unstructured":"Broccoll, V., Boncinelli, E. and Wurst, W.(1999). The caudal limit of Otx2 expression positions the isthmic organizer, Nature401,164-168.","DOI":"10.1038\/43670"},{"key":"2021042612032339000_REF4","doi-asserted-by":"crossref","unstructured":"Castella, P., Wagner, J. A. and Caudy, M.(1999). Regulation of hippocampal neuronal differentiation by the basic helix-loop-helix transcription factors HES-1 and MASH-1. J. Neurosci. Res.56,229-240.","DOI":"10.1002\/(SICI)1097-4547(19990501)56:3<229::AID-JNR2>3.0.CO;2-Z"},{"key":"2021042612032339000_REF5","doi-asserted-by":"crossref","unstructured":"Castella, P., Sawai, S., Nakao, K., Wagner, J. A. and Caudy,M. (2000). HES-1 repression of differetiation and proliferation in PC12 cells: role for the helix 3-helix 4 domain in transcription repression. Mol. Cell. Biol.20,6170-6183.","DOI":"10.1128\/MCB.20.16.6170-6183.2000"},{"key":"2021042612032339000_REF6","doi-asserted-by":"crossref","unstructured":"Chen, H., Thiagalingam, A., Chopra, H., Borges, M. W., Feder, J. N., Nelkin, B. D., Baylin, S. B. and Ball, D. W. (1997). Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. Proc. Natl. Acad. Sci. USA94,5355-5360.","DOI":"10.1073\/pnas.94.10.5355"},{"key":"2021042612032339000_REF7","doi-asserted-by":"crossref","unstructured":"Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F.,Roberts, J. M. and Sherr, C. J. (1999). The p21Cip1 and p27Kip1 CDK `inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J.18,1571-1583.","DOI":"10.1093\/emboj\/18.6.1571"},{"key":"2021042612032339000_REF8","doi-asserted-by":"crossref","unstructured":"Cheng, Y.-C., Amoyel, M., Qiu, X., Jiang, Y.-J., Xu, Q.,Wilkinson, D. G. (2004). Notch activation regulates the segregation and differentiation of rhombomere boundary cells in the zebrafish hindbrain. Dev. Cell6,539-550.","DOI":"10.1016\/S1534-5807(04)00097-8"},{"key":"2021042612032339000_REF9","doi-asserted-by":"crossref","unstructured":"Ema, M., Morita, M., Ikawa, S., Tanaka, M., Matsuda, Y., Gotoh,O., Saijoh, Y., Fujii, H., Hamada, H., Kikuchi, Y. et al.(1996). Two new members of the murine Sim gene family are transcriptional repressors and show different expression patterns during mouse embryogenesis. Mol. Cell. Biol.16,5865-5875.","DOI":"10.1128\/MCB.16.10.5865"},{"key":"2021042612032339000_REF10","doi-asserted-by":"crossref","unstructured":"Geling, A., Plessy, C., Rastegar, S., Strahle, U. and Bally-Cuif, L. (2004). Her5 acts as a prepattern factor that blocks neurogenin1 and coe2 expression upstream of Notch to inhibit neurogenesis at the midbrain-hindbrain boundary. Development131,1993-2006.","DOI":"10.1242\/dev.01093"},{"key":"2021042612032339000_REF11","doi-asserted-by":"crossref","unstructured":"Guthrie, S., Butcher, M. and Lumsden, A.(1991). Patterns of cell division and interkinetic nuclear migration in the chick embryo hindbrain. J. Neurobiol.22,742-754.","DOI":"10.1002\/neu.480220709"},{"key":"2021042612032339000_REF12","doi-asserted-by":"crossref","unstructured":"Hartman, J., Mu\u0308ller, P., Foster, J. S., Wimalasena, J. and Gustafsson, J.-A\u030a. (2004). HES-1 inhibits 17\u03b2-estradiol and heregulin-\u03b21-mediated upregulation of E2F-1. Oncogene23,8826-8833.","DOI":"10.1038\/sj.onc.1208139"},{"key":"2021042612032339000_REF13","doi-asserted-by":"crossref","unstructured":"Hatakeyama, J. and Kageyama, R. (2002). Retrovirus-mediated gene transfer to retinal explants. Methods28,387-395.","DOI":"10.1016\/S1046-2023(02)00257-8"},{"key":"2021042612032339000_REF14","doi-asserted-by":"crossref","unstructured":"Hatakeyama, J., Bessho, Y., Katoh, K., Ookawara, S., Fujioka,M., Guillemot, F. and Kageyama, R. (2004). Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development131,5539-5550.","DOI":"10.1242\/dev.01436"},{"key":"2021042612032339000_REF15","doi-asserted-by":"crossref","unstructured":"Hatakeyama, J., Sakamoto, S. and Kageyama, R.(2006). Hes1 and Hes5 regulate the development of the cranial and spinal nerve systems. Dev. Neurosci.28,92-101.","DOI":"10.1159\/000090756"},{"key":"2021042612032339000_REF16","doi-asserted-by":"crossref","unstructured":"Hirata, H., Ohtsuka, T., Bessho, Y. and Kageyama, R.(2000). Generation of structurally and functionally distinct factors from the basic helix-loop-helix gene Hes3 by alternative first exons. J. Biol. Chem.275,19083-19089.","DOI":"10.1074\/jbc.M001075200"},{"key":"2021042612032339000_REF17","doi-asserted-by":"crossref","unstructured":"Hirata, H., Tomita, K., Bessho, Y. and Kageyama, R.(2001). Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid\/hindbrain. EMBO J.20,4454-4466.","DOI":"10.1093\/emboj\/20.16.4454"},{"key":"2021042612032339000_REF18","doi-asserted-by":"crossref","unstructured":"Hirata, H., Yoshiura, S., Ohtsuka, T., Bessho, Y., Harada, T.,Yoshikawa, K. and Kageyama, R. (2002). Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science298,840-843.","DOI":"10.1126\/science.1074560"},{"key":"2021042612032339000_REF19","unstructured":"Hojo, M., Ohtsuka, T., Hashimoto, N., Gradwohl, G., Guillemot,F. and Kageyama, R. (2000). Glial cell fate specification modulated by the bHLH gene Hes5 in mouse retina. Development127,2515-2522."},{"key":"2021042612032339000_REF20","doi-asserted-by":"crossref","unstructured":"Irvine, K. D. and Rauskolb, C. (2001). Boundaries in development: formation and function. Annu. Rev. Cell Dev. Biol.17,189-214.","DOI":"10.1146\/annurev.cellbio.17.1.189"},{"key":"2021042612032339000_REF21","doi-asserted-by":"crossref","unstructured":"Jarriault, S., Brou, C., Logeat, F., Schroeter, E. H., Kopan, R. and Israel, A. (1995). Signalling downstream of activated mammalian Notch. Nature377,355-358.","DOI":"10.1038\/377355a0"},{"key":"2021042612032339000_REF22","doi-asserted-by":"crossref","unstructured":"Joyner, A. L., Liu, A. and Millet, S. (2000). Otx2, Gbx2 and Fgf8 interact to position and maintain a mid-hindbrain organizer. Curr. Opin. Cell Biol.12,736-741.","DOI":"10.1016\/S0955-0674(00)00161-7"},{"key":"2021042612032339000_REF23","doi-asserted-by":"crossref","unstructured":"Kabos, P., Kabosova, A. and Neuman, A. (2002). Blocking HES1 expression initiates GABAergic differentiation and induces the expression of p21CIP1\/WAF1 in human neural stem cells. J. Biol. Chem.277,8763-8766.","DOI":"10.1074\/jbc.C100758200"},{"key":"2021042612032339000_REF24","doi-asserted-by":"crossref","unstructured":"Kageyama, R. and Nakanishi, S. (1997). Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. Curr. Opin. Genet. Dev.7, 659-665.","DOI":"10.1016\/S0959-437X(97)80014-7"},{"key":"2021042612032339000_REF25","doi-asserted-by":"crossref","unstructured":"Kahane, N. and Kalcheim, C. (1998). 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Neurosci.24,869-896.","DOI":"10.1146\/annurev.neuro.24.1.869"},{"key":"2021042612032339000_REF32","doi-asserted-by":"crossref","unstructured":"Lumsden, A. and Keynes, R. (1989). Segmental patterns of neuronal development in the chick hindbrain. Nature337,424-428.","DOI":"10.1038\/337424a0"},{"key":"2021042612032339000_REF33","doi-asserted-by":"crossref","unstructured":"Lumsden, A. and Krumlauf, R. (1996). Patterning the vertebrate neuraxis. Science274,1109-1115.","DOI":"10.1126\/science.274.5290.1109"},{"key":"2021042612032339000_REF34","doi-asserted-by":"crossref","unstructured":"Masamizu, Y., Ohtsuka, T., Takashima, Y., Nagahara, H.,Takenaka, Y., Yoshikawa, K., Okamura, H. and Kageyama, R.(2006). Real-time imaging of the somite segmentation clock:revelation of unstable oscillators in the individual presomitic mesoderm cells. Proc. Natl. Acad. Sci. USA103,1313-1318.","DOI":"10.1073\/pnas.0508658103"},{"key":"2021042612032339000_REF35","doi-asserted-by":"crossref","unstructured":"Mason, I., Chambers, D., Shamim, H., Walshe, J. and Irving,C. (2000). Regulation and function of FGF8 in patterning of midbrain and anterior hindbrain. Biochem. Cell Biol.78,577-584.","DOI":"10.1139\/o00-073"},{"key":"2021042612032339000_REF36","doi-asserted-by":"crossref","unstructured":"Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E. and Joyner, A. L. (1999). A role for Gbx2 in repression of Otx2 and positioning the mid\/hindbrain organizer. Nature401,161-164.","DOI":"10.1038\/43664"},{"key":"2021042612032339000_REF37","doi-asserted-by":"crossref","unstructured":"Momota, H. and Holland, E. C. (2005). Bioluminescence technology for imaging cell proliferation. Curr. Opin. 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Mash1 and Math3 are required for development of branchiomotor neurons and maintenance of neural progenitors. J. Neurosci.25,5857-5865.","DOI":"10.1523\/JNEUROSCI.4621-04.2005"},{"key":"2021042612032339000_REF41","doi-asserted-by":"crossref","unstructured":"Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S.,Guillemot, F. and Kageyama, R. (1999). Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation. EMBO J.18,2196-2207.","DOI":"10.1093\/emboj\/18.8.2196"},{"key":"2021042612032339000_REF42","doi-asserted-by":"crossref","unstructured":"Ohtsuka, T., Sakamoto, M., Guillemot, F. and Kageyama, R.(2001). Roles of the basic helix-loop-helix genes Hes1and Hes5 in expansion of neural stem cells of the developing brain. J. Biol. Chem.276,30467-30474.","DOI":"10.1074\/jbc.M102420200"},{"key":"2021042612032339000_REF43","doi-asserted-by":"crossref","unstructured":"Ohtsuka, T., Imayoshi, I., Shimojo, H., Nishi, E., Kageyama, R. and McConnell, S. K. (2006). Visualization of embryonic neural stem cells using Hes promoters in transgenic mice. Mol. Cell. Neurosci.31,109-122.","DOI":"10.1016\/j.mcn.2005.09.006"},{"key":"2021042612032339000_REF44","doi-asserted-by":"crossref","unstructured":"Placzek, M. and Briscoe, J. (2005). The floor plate: multiple cells, multiple signals. Nat. Rev. Neurosci.6,230-240.","DOI":"10.1038\/nrn1628"},{"key":"2021042612032339000_REF45","doi-asserted-by":"crossref","unstructured":"Rhinn, M. and Brand, M. (2001). The midbrain-hindbrain boundary organizer. Curr. Opin. Neurobiol.11,34-42.","DOI":"10.1016\/S0959-4388(00)00171-9"},{"key":"2021042612032339000_REF46","doi-asserted-by":"crossref","unstructured":"Sasai, Y., Kageyama, R., Tagawa, Y., Shigemoto, R. and Nakanishi, S. (1992). Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. 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V., Trokovic, N., Wurst, W. and Partanen,J. (2005). Fgfr1-dependent boundary cells between developing mid- and hindbrain. Dev. Biol.278,428-439.","DOI":"10.1016\/j.ydbio.2004.11.024"},{"key":"2021042612032339000_REF53","doi-asserted-by":"crossref","unstructured":"Vernay, B., Koch, M., Vaccarino, F., Briscoe, J., Simeone, A.,Kageyama, R. and Ang, S. L. (2005). Otx2 regulates subtype specification and neurogenesis in the midbrain. J. Neurosci.25,4856-4867.","DOI":"10.1523\/JNEUROSCI.5158-04.2005"},{"key":"2021042612032339000_REF54","doi-asserted-by":"crossref","unstructured":"Wurst, W. and Bally-Cuif, L. (2001). Neural plate patterning: upstream and downstream of the isthmic organizer. Nat. Rev. Neurosci.2,99-108.","DOI":"10.1038\/35053516"},{"key":"2021042612032339000_REF55","doi-asserted-by":"crossref","unstructured":"Zeltser, L. M. (2005). Shh-dependent formation of the ZLI is opposed by signals from the dorsal diencephalon. 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