Gene regulatory network governing the neural plate development from the epiblast

2013 Fiscal Year Final Research Report

• Project/Area Number: 22247035
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Osaka University
• Principal Investigator: KONDOH Hisato 大阪大学, 生命機能研究科, 教授 (70127083)
• Co-Investigator(Renkei-kenkyūsha): KAMACHI Yusuke 大阪大学, 大学院生命機能研究科, 准教授 (90263334) ; UCHIKAWA Masanori 大阪大学, 大学院生命機能研究科, 助教 (80346147) ; TAKEMOTO Tatsuya 大阪大学, 大学院生命機能研究科, 助教 (30443899)
• Project Period (FY): 2010-05-31 – 2014-03-31
• Keywords: エピブラスト / 前部神経板 / 後部神経板 / 転写因子 / Sox2 / 幹細胞 / 原腸陥入

Research Abstract

We investigated the regulatory mechanisms that underlie the derivation of the neural plates (neural precursors) from the pan-somatic tissue precursor epiblast. We took advantage of mutant mouse embryos and epiblast stem cells under culture conditions.
The anterior neural plate, as marked by Sox2 N2 enhancer activity, was derived directly from the epiblast through the cooperative action of transcription factors that promote neural development but repress the development of all non-neural lineages. By contrast, the posterior neural plate, as marked by Sox2 N1 enhancer activity, developed through neuro-mesodermal bipotential precursors named "axial stem cells". Tbx6-dependent repression of the N1 enhancer was required for mesodermal development. These new findings revise the classical view of somatic cell lineage separation, where germ layer separation was assumed to be the essential first step.

Research Products

• [Journal Article] Dkk1-dependent inhibition of Wnt signaling activates Hesx1 expression through its 5' enhancer and directs forebrain precursor development (2014)
  • Author(s): Matsuda K, Kondoh H.
  • Journal Title: Genes Cells Volume: 19 Pages: 374-385
  • DOI: 10.1111/gtc.12136
  • Peer Reviewed
• [Journal Article] Lovell-Badge R, Takemoto T, Kondoh H. Regulation of mesodermal precursor production by low-level expression of B1 Sox genes in the caudal lateral epiblast (2014)
  • Author(s): Yoshida M, Uchikawa M, Rizzoti K
  • Journal Title: Mech Dev Volume: 132 Pages: 59-68
  • DOI: 10.1016/j.mod.2014.01.003
  • Peer Reviewed
• [Journal Article] Sox proteins : regulators of cell fate specification and differentiation (2013)
  • Author(s): Kamachi, Y, Kondoh, H
  • Journal Title: Development Volume: 140 Pages: 4129-4244
  • DOI: 10.1242/dev.091793
  • Peer Reviewed
• [Journal Article] Progression of neurogenesis in the inner ear requires inhibition of Sox2 transcription by neurogenin1 and neurod1 (2013)
  • Author(s): Evsen, L., Sugahara, S., Uchikawa, M., Kondoh, H., Wu, DK.
  • Journal Title: J Neurosci Volume: 33 Pages: 879-890
  • DOI: 10.1523/JNEUROSCI.4030-12.2013
  • Peer Reviewed
• [Journal Article] A systematic survey and characterization of enhancers that regulate Sox3 in neurosensory development in comparison with Sox2 enhancers (2012)
  • Author(s): Nishimura, N., Kamimura, Y., Ishida, Y., Takemoto, T., Kondoh, H., Uchikawa, M.
  • Journal Title: Biology Volume: 1 Pages: 714-735
  • DOI: 10.3390/biology1030714
  • Peer Reviewed
• [Journal Article] Axial stem cells deriving both posterior neural and mesodermal tissues during gastrulation (2012)
  • Author(s): Kondoh, H., Takemoto, T.
  • Journal Title: Curr Opin Genet Dev Volume: 22 Pages: 374-380
  • DOI: 10.1016/j.gde.2012.03.006
  • Peer Reviewed
• [Journal Article] Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells (2012)
  • Author(s): Iwafuchi-Doi, M., Matsuda, K., Murakami, K., Niwa, H., Tesar, P. J., Aruga, J., Matsuo, I., Kondoh, H.
  • Journal Title: Development Volume: 139 Pages: 3926-3937
  • DOI: 10.1242/dev.085936
  • Peer Reviewed
• [Journal Article] B1 and B2 Sox gene expression during neural plate development in chicken and mouse embryos : universal versus species-dependent features (2011)
  • Author(s): Uchikawa, M., Yoshida, M., Iwafuchi-Doi, M., Matsuda, K., Ishida, Y., Takemoto, T. Kondoh, H.
  • Journal Title: Dev Growth Differ Volume: 53 Pages: 761-771
  • DOI: 10.1111/j.1440-169X.2011.01286.x.
  • Peer Reviewed
• [Journal Article] Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells (2011)
  • Author(s): Takemoto, T., Uchikawa, M., Yoshida, M., Bell, D. M., Lovell-Badge, R., Papaioannou, V. E., Kondoh, H.
  • Journal Title: Nature Volume: 470 Pages: 394-398
  • DOI: 10.1038/nature09729
  • Peer Reviewed
• [Journal Article] The Pou5f1/Pou3f- dependent but SoxB-independent regulation of conserved enhancer N2 initiates Sox2 expression during epiblast to neural plate stages in vertebrates (2011)
  • Author(s): Iwafuchi-Doi, M., Yoshida, Y., Onichtchouk, D., Leichsenring, M., Driever, W., Takemoto, T., Uchikawa, M., Kamachi, Y., Kondoh, H.
  • Journal Title: Dev Biol Volume: 352 Pages: 354-366
  • DOI: 10.1016/j.ydbio.2010.12.027
  • Peer Reviewed
• [Journal Article] SOX-partner code for cell specification: Regulatory target selection and underlying molecular mechanisms (2010)
  • Author(s): Kondoh, H., Kamachi, Y.
  • Journal Title: Int J Biochem Cell Biol Volume: 42 Pages: 391-399
  • DOI: 10.1016/j.biocel.2009.09.003
  • Peer Reviewed
• [Presentation] Inhibitory mechanisms required for deriving specific somatic lineages from the epiblast (2013)
  • Author(s): Kondoh, H
  • Organizer: The 61^<st> NIBB conference "Cellular Community in Mammalian Embryogenesis"
  • Place of Presentation: Okazaki, Japan
  • Year and Date: 20130710-12
• [Presentation] Distinct regulatory mechanisms for the genesis of anterior and posterior neural plates, the primordia for brain and spinal cord (2013)
  • Author(s): Kondoh H
  • Organizer: Symposium on Sensory Systems & Neural Circuits
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20130211-12
• [Presentation] Generation of neural primordia in vertebrate embryos by mechanisms that challenge the classical models (2011)
  • Author(s): Kondoh H
  • Organizer: Commemorative Symposium for the 27th International Prize for Biology "Genetic Regulation of Development"
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20111130-1201
• [Presentation] Distinct regulatory mechanisms for the genesis of anterior and posterior neural plates (2011)
  • Author(s): Kondoh H
  • Organizer: Hong Kong Society for Developmental Biology Symposium "From Embryology to Disease Mechanisms"
  • Place of Presentation: Hong Kong
  • Year and Date: 20111126-27
• [Presentation] Generation of neural primordia in vertebrate embryos by mechanisms that challenge the classical models (2011)
  • Author(s): Kondoh H
  • Organizer: "Cold Spring Harbor Asia Conference on Developmental Control of Sex, Growth and Cellular Fate"
  • Place of Presentation: Suzhou, China
  • Year and Date: 20111011-15
• [Remarks] ① 論文⑨に関する新聞報道(2011年2月17日):毎日新聞、日本経済新聞、読売新聞、朝日新聞、産經新聞ほか。
• [Remarks] ② 本研究の科研費NEWS での紹介:2011年度 VOL.2,最新の研究成果トピックス「三胚葉モデル」にかわる新しい機構による、神経系の成立。