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      The Shh coreceptor Cdo is required for differentiation of midbrain dopaminergic neurons.

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          Abstract

          Sonic hedgehog (Shh) signaling is required for numerous developmental processes including specification of ventral cell types in the central nervous system such as midbrain dopaminergic (DA) neurons. The multifunctional coreceptor Cdo increases the signaling activity of Shh which is crucial for development of forebrain and neural tube. In this study, we investigated the role of Cdo in midbrain DA neurogenesis. Cdo and Shh signaling components are induced during neurogenesis of embryonic stem (ES) cells. Cdo(-/-) ES cells show reduced neuronal differentiation accompanied by increased cell death upon neuronal induction. In addition, Cdo(-/-) ES cells form fewer tyrosine hydroxylase (TH) and microtubule associated protein 2 (MAP2)-positive DA neurons correlating with the decreased expression of key regulators of DA neurogenesis, such as Shh, Neurogenin2, Mash1, Foxa2, Lmx1a, Nurr1 and Pitx3, relative to the Cdo(+/+) ES cells. Consistently, the Cdo(-/-) embryonic midbrain displays a reduction in expression of TH and Nurr1. Furthermore, activation of Shh signaling by treatment with Purmorphamine (Pur) restores the DA neurogenesis of Cdo(-/-) ES cells, suggesting that Cdo is required for the full Shh signaling activation to induce efficient DA neurogenesis.

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          Author and article information

          Journal
          Stem Cell Res
          Stem cell research
          1876-7753
          1873-5061
          Sep 2014
          : 13
          : 2
          Affiliations
          [1 ] Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
          [2 ] Research Center for Cell Fate Control, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
          [3 ] Department of Physiology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Republic of Korea.
          [4 ] Research Center for Cell Fate Control, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: gbae@sm.ac.kr.
          [5 ] Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. Electronic address: kangj01@skku.edu.
          Article
          S1873-5061(14)00085-3
          10.1016/j.scr.2014.07.004
          25117422
          Copyright © 2014. Published by Elsevier B.V.

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