Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells
Author:
Ono Yuichi1, Nakatani Tomoya1, Sakamoto Yoshimasa1, Mizuhara Eri1, Minaki Yasuko1, Kumai Minoru1, Hamaguchi Akiko1, Nishimura Miyuki1, Inoue Yoko1, Hayashi Hideki2, Takahashi Jun2, Imai Toshio1
Affiliation:
1. KAN Research Institute Inc., KobeMI R&D Center 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. 2. Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Abstract
Directed differentiation and purification of mesencephalic dopaminergic(mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for Parkinson's disease. Although recent studies have identified the factors that regulate mesDA neuron development, the mechanisms underlying mesDA neuron specification are not fully understood. Recently, it has been suggested that mesencephalic floor plate (FP) cells acquire neural progenitor characteristics to generate mesDA neurons. Here, we directly examined this in a fate mapping experiment using fluorescence-activated cell sorting (FACS) with an FP cell-specific surface marker, and demonstrate that mesencephalic FP cells have neurogenic activity and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have no neurogenic potential, as previously thought. Analysis of dreher mutant mice carrying a mutation in the Lmx1a locus and transgenic mice ectopically expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior identity that confers neurogenic activity to FP cells and specifies a mesDA fate, at least in part through the induction of Lmx1a. We further show that FACS can isolate mesDA progenitors, a suitable transplantation material, from embryonic stem cell-derived neural cells. Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference31 articles.
1. Andersson, E., Jensen, J. B., Parmar, M., Guillemot, F. and Bjorklund, A. (2006a). Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development133,507-516. 2. Andersson, E., Tryggvason, U., Deng, Q., Friling, S.,Alekseenko, Z., Robert, B., Perlmann, T. and Ericson, J.(2006b). Identification of intrinsic determinants of midbrain dopamine neurons. Cell124,393-405. 3. Barberi, T., Klivenyi, P., Calingasan, N. Y., Lee, H., Kawamata,H., Loonam, K., Perrier, A. L., Bruses, J., Rubio, M. E., Topf, N. et al.(2003). Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice. Nat. Biotechnol. 21,1200-1207. 4. Brodski, C., Weisenhorn, D. M., Signore, M., Sillaber, I.,Oesterheld, M., Broccoli, V., Acampora, D., Simeone, A. and Wurst, W.(2003). Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J. Neurosci. 23,4199-4207. 5. Chizhikov, V. V. and Millen, K. J. (2004a). Control of roof plate development and signaling by Lmx1b in the caudal vertebrate CNS. J. Neurosci. 24,5694-5703.
Cited by
275 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|