journal article
Nov 01, 2003
Xrx1controls proliferation and neurogenesis inXenopusanterior neural plate
Abstract
In Xenopus neuroectoderm, posterior cells start differentiating at the end of gastrulation, while anterior cells display an extended proliferative period and undergo neurogenesis only at tailbud stage. Recent studies have identified several important components of the molecular pathways controlling posterior neurogenesis, but little is known about those controlling the timing and positioning of anterior neurogenesis. We investigate the role of Xrx1, a homeobox gene required for eye and anterior brain development, in the control of proliferation and neurogenesis of the anterior neural plate. Xrx1 is expressed in the entire proliferative region of the anterior neural plate delimited by cells expressing the neuronal determination gene X-ngnr-1, the neurogenic gene X-Delta-1, and the cell cycle inhibitor p27Xic1. Positive and negative signals position Xrx1 expression to this region. Xrx1 is activated by chordin and Hedgehog gene signaling, which induce anterior and proliferative fate, and is repressed by the differentiation-promoting activity of neurogenin and retinoic acid. Xrx1 is required for anterior neural plate proliferation and, when overexpressed, induces proliferation, inhibits X-ngnr-1, X-Delta-1and N-tubulin and counteracts X-ngnr-1- and retinoic acid-mediated differentiation. We find that Xrx1 does not act by increasing lateral inhibition but by inducing the antineurogenic transcriptional repressors Xhairy2 and Zic2, and by repressing p27Xic1. The effects of Xrx1 on proliferation,neurogenesis and gene expression are restricted to the most rostral region of the embryo, implicating this gene as an anterior regulator of neurogenesis.
Topics
No keywords indexed for this article. Browse by subject →
References
55
[1]
Andreazzoli, M., Gestri, G., Angeloni, D., Menna, E. and Barsacchi, G. (1999). Role of Xrx1 in Xenopus eye and anterior brain development. Development126,2451-2460.
10.1242/dev.126.11.2451
[2]
Bellefroid, E. J., Kobbe, A., Gruss, P., Pieler, T., Gurdon, J. B. and Papalopulu, N. (1998). Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification. EMBO J.17,191-203.
10.1093/emboj/17.1.191
[3]
Bernier, G., Panitz, F., Zhou, X., Hollemann, T., Gruss, P. and Pieler, T. (2000). Expanded retina territory by midbrain transformation upon overexpression of Six6 (Optx2) in Xenopus embryos. Mech. Dev.93, 59-69.
10.1016/s0925-4773(00)00271-9
[4]
Bourguignon, C., Li, J. and Papalopulu, N.(1998). XBF-1, a winged helix transcription factor with dual activity, has a role in positioning neurogenesis in Xenopuscompetent ectoderm. Development125,4889-4900.
[5]
Brewster, R., Lee, J. and Ruiz i Altaba, A.(1998). Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature393,579-583.
10.1038/31242
[6]
Brown, S. A., Warburton, D., Brown, L. Y., Yu, C. Y., Roeder, E. R., Stengel-Rutkowski, S., Hennekam, R. C. and Muenke, M.(1998). Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nat. Genet.2,180-183.
10.1038/2484
[7]
Carruthers, S., Mason, J. and Papalopulu, N.(2003). Depletion of the cell-cycle inhibitor p27(Xic1) impairs neuronal differentiation and increases the number of ElrC(+) progenitor cells in Xenopus tropicalis. Mech. Dev.120,607-616.
10.1016/s0925-4773(03)00010-8
[8]
Casarosa, S., Andreazzoli, M., Simeone, A. and Barsacchi, G.(1997). Xrx1, a novel Xenopus homeobox gene expressed during eye and pineal gland development. Mech. Dev.61,187-198.
10.1016/s0925-4773(96)00640-5
[9]
Cavodeassi, F., Modolell, J. and Gomez-Skarmeta, J. L.(2001). The Iroquois family of genes: from body building to neural patterning. Development128,2847-2855.
10.1242/dev.128.15.2847
[10]
Chen, Y., Huang, L. and Solrush, M. (1994). A concentration gradient of retinoids in the early Xenopus laevisembryo. Dev. Biol.161,70-76.
10.1006/dbio.1994.1008
[11]
Chen, Y., Pollet, N., Niehrs, C. and Pieler, T.(2001). Increased XRALDH2 activity has a posteriorizing effect on the central nervous system of Xenopus embryos. Mech. Dev.101,91-103.
10.1016/s0925-4773(00)00558-x
[12]
Chitnis, A., Henrique, D., Lewis, J., Ish-Horowicz, D. and Kintner, C. (1995). Primary neurogenesis in Xenopusembryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature375,761-766.
10.1038/375761a0
[13]
Chitnis, A. B. (1999). Control of neurogenesis- lessons from frogs, fish and flies. Curr. Opin. Neurobiol.9,18-25.
10.1016/s0959-4388(99)80003-8
[14]
Chuang, J. C. and Raymond, P. A. (2001). Zebrafish genes rx1 and rx2 help define the region of forebrain that gives rise to retina. Dev. Biol.231, 13-30.
10.1006/dbio.2000.0125
[15]
Davis, R. L., Turner, D. L., Evans, L. M. and Kirschner, M. W. (2001). Molecular targets of vertebrate segmentation: two mechanisms control segmental expression of Xenopus hairy2 during somite formation. Dev. Cell1, 553-565.
10.1016/s1534-5807(01)00054-5
[16]
Dawson, S. R., Turner, D. L., Weintraub, H. and Parkhurst, S. M. (1995). Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression. Mol. Cell. Biol.15,6923-6931.
10.1128/mcb.15.12.6923
[17]
de la Calle-Mustienes, E., Glavic, A., Modolell, J. and Gomez-Skarmeta, J. L. (2002). Xiro homeoproteins coordinate cell cycle exit and primary neuron formation by upregulating neuronal-fate repressors and downregulating the cell-cycle inhibitor XGadd45-gamma. Mech. Dev.119, 69-80.
10.1016/s0925-4773(02)00296-4
[18]
Eagleson, G. W. and Harris, W. A. (1990). Mapping of the presumptive brain regions in the neural plate of Xenopus laevis. J. Neurobiol.21,427-440.
10.1002/neu.480210305
[19]
Eagleson, G, Ferreiro, B. and Harris, W. A.(1995). Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain. J. Neurobiol.2, 146-158.
10.1002/neu.480280203
[20]
Ekker, S. C., McGrew, L. L., Lai, C. J., Lee, J. J., von Kessler, D. P., Moon, R. T. and Beachy, P. A. (1995). Distinct expression and shared activities of members of the hedgehoggene family of Xenopus laevis. Development121,2337-2347.
[21]
Ermakova, G. V., Alexandrova, E. M., Kazanskaya, O. V.,Vasiliev, O. L., Smith, M. W. and Zaraisky, A. G.(1999). The homeobox gene, Xanf-1, can control both neural differentiation and patterning in the presumptive anterior neurectoderm of the Xenopus laevis embryo. Development126,4513-4523.
10.1242/dev.126.20.4513
[22]
Fantl, V., Stamp, G., Andrews, A., Rosewell, I. and Dickson,C. (1995). Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev.9,2364-2372.
10.1101/gad.9.19.2364
[23]
Fisher, A. and Caudy, M. (1998). The function of hairy-related bHLH repressor proteins in cell fate decisions. BioAssays20,298-306.
10.1002/(sici)1521-1878(199804)20:4<298::aid-bies6>3.0.co;2-m
[24]
Franco, P. G., Paganelli, A. R., Lopez, S. L. and Carrasco, A. E. (1999). Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis. Development126,4257-4265.
10.1242/dev.126.19.4257
[25]
Furukawa, T., Mukherjee, S., Bao, Z. Z., Morrow, E. M. and Cepko, C. L. (2000). rax, Hes1, and Notch1 promote the formation of Muller glia by postnatal retinal progenitor cells. Neuron26,383-394.
10.1016/s0896-6273(00)81171-x
[26]
Gomez-Skarmeta, J. L., del Corral, R. D., de la Calle-Mustienes,E., Ferre- Marco, D. and Modolell, J. (1996). Araucan and caupolican, two members of the novel Iroquois complex, encode homeoproteins that control proneural and vein-forming genes. Cell85, 95-105.
10.1016/s0092-8674(00)81085-5
[27]
Gomez-Skarmeta, J. L., Glavic, A., de la Calle-Mustienes, E.,Modolell, J. and Mayor, R. (1998). Xiro, a Xenopus homologue of the Drosophila Iroquois complex genes,controls development at the neural plate. EMBO J.17,181-190.
10.1093/emboj/17.1.181
[28]
Hardcastle, Z. and Papalopulu, N. (2000). Distinct effects of XBF-1 in regulating the cell cycle inhibitor p27Xic1 and imparting a neural fate. Development127,1303-1314.
10.1242/dev.127.6.1303
[29]
Harland, R. M. (1991). In situ hybridization:an improved whole-mount method for Xenopus embryos. Methods Cell Biol.36,685-695.
10.1016/s0091-679x(08)60307-6
[30]
Harris, W. A. and Hartenstein, V. (1991). Neuronal determination without cell division in Xenopus laevis. Neuron6,499-515.
10.1016/0896-6273(91)90053-3
[31]
Hartenstein, V. (1989). Early neurogenesis in Xenopus: the spatio-temporal pattern of proliferation and cell lineages in the embryonic spinal cord. Neuron3, 399-411.
10.1016/0896-6273(89)90200-6
[32]
Hartenstein, V. (1993). Early pattern of neuronal differentiation in the Xenopus embryonic brainstem and spinal cord. J. Comp. Neurol.328,213-231.
10.1002/cne.903280205
[33]
Heasman, J., Kofron, M. and Wylie, C. (2000). Beta-catenin signaling activity dissected in the early Xenopusembryo: a novel antisense approach. Dev. Biol.222,124-134.
10.1006/dbio.2000.9720
[34]
Hollemann, T., Chen, Y., Grunz, H. and Pieler, T.(1998). Regionalized metabolic activity establishes boundaries of retinoic acid signalling. EMBO J.17,7361-7372.
10.1093/emboj/17.24.7361
[35]
Itoh, M., Kudoh, T., Dedekian, M., Kim, C. H. and Chitnis, A. B. (2002). A role for iro1 and iro7 in the establishment of an anteroposterior compartment of the ectoderm adjacent to the midbrain-hindbrain boundary. Development129,2317-2327.
[36]
Kenyon, K. L., Zaghloul, N. and Moody, S. A.(2001). Transcription factors of the anterior neural plate alter cell movements of epidermal progenitors to specify a retinal fate. Dev. Biol.240,77-91.
10.1006/dbio.2001.0464
[37]
Koyano-Nakagawa, N., Kim, J., Anderson, D. and Kintner, C.(2000). Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation. Development127,4203-4216.
10.1242/dev.127.19.4203
[38]
Loosli, F., Winkler, S., Burgtorf, C., Wurmbach, E., Ansorge,W., Henrich, T., Grabher, C., Arendt, D., Carl, M., Krone, A.,Grzebisz, E. and Wittbrodt, J. (2001). Medaka eyeless is the key factor linking retinal determination and eye growth. Development128,4035-4044.
[39]
Ma, Q., Kintner, C. and Anderson, D. J. (1996). Identification of neurogenin, a vertebrate neuronal determination gene. Cell87,43-52.
10.1016/s0092-8674(00)81321-5
[40]
Mathers, P. H., Grinberg, A., Mahon, K. A. and Jamrich, M.(1997). The Rx homeobox gene is essential for vertebrate eye development. Nature387,603-607.
10.1038/42475
[41]
Mizuseki, K., Kishi, M., Matsui, M., Nakanishi, S. and Sasai,Y. (1998). Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. Development125,579-587.
10.1242/dev.125.4.579
[42]
Nakata, K., Nagai, T., Aruga, J. and Mikoshiba, K.(1997). Xenopus Zic3, a primary regulator both in neural and neural crest development. Proc. Natl. Acad. Sci. USA94,11980-11985.
10.1073/pnas.94.22.11980
[43]
Newport, J. and Kirschner, M. (1982). A major developmental transition in early Xenopus embryos. Cell30,687-696.
10.1016/0092-8674(82)90273-2
[44]
Nieuwkoop, P. D. and Faber, J. (1967).Normal Table of Development of Xenopus laevis (Daudin). North-Holland, Amsterdam.
[45]
Papalopulu, N. and Kintner, C. (1996). A posteriorizing factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopusneuroectoderm. Development122,3409-3418.
[46]
Saka, Y. and Smith, J. C. (2001). Spatial and temporal patterns of cell division during early Xenopusembryogenesis. Dev. Biol.229,307-318.
10.1006/dbio.2000.0101
[47]
Sasai, Y., Lu, B., Steinbeisser, H. and De Robertis, E. M.(1995). Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus. Nature376,333-336.
10.1038/376333a0
[48]
Sasai, Y. and de Robertis, E. M. (1997). Ectodermal patterning in vertebrate embryos. Dev. Biol.182,5-20.
10.1006/dbio.1996.8445
[49]
Sharpe, C. and Goldstone, K. (2000). The control of Xenopus embryonic primary neurogenesis is mediated by retinoid signaling in the neuroectoderm. Mech. Dev.91, 69-80.
10.1016/s0925-4773(99)00273-7
[50]
Spemann, H. (1938). Embryonic Induction and Development. New Haven, CT: Yale University Press.
Showing 50 of 55 references
Cited By
65
Emerging roles for zic genes in early development
Developmental Dynamics
Christa S. Merzdorf · 2007
Metrics
65
Citations
55
References
Details
- Published
- Nov 01, 2003
- Vol/Issue
- 130(21)
- Pages
- 5143-5155
Authors
Cite This Article
Massimiliano Andreazzoli, Gaia Gestri, Federico Cremisi, et al. (2003). Xrx1controls proliferation and neurogenesis inXenopusanterior neural plate. Development, 130(21), 5143-5155. https://doi.org/10.1242/dev.00665
Related
You May Also Like
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
Andrea H. Brand, Norbert Perrimon · 1993
8,326 citations
Third-generation
in situ
hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust
Harry M. T. Choi, Maayan Schwarzkopf · 2018
1,486 citations
Cellular organisation of the Arabidopsis thaliana root
Liam Dolan, Kees Janmaat · 1993
1,224 citations
Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst
Dan Strumpf, Chai-An Mao · 2005
987 citations