The striatum is a central regulator of behavior and motor function through the actions of D1 and D2 medium-sized spiny neurons (MSNs), which arise from a common lateral ganglionic eminence (LGE) progenitor. The molecular mechanisms of cell fate specification of these two neuronal subtypes are incompletely understood. Here, we found that deletion of Meis2, which is highly expressed in the LGE and derivatives led to a large reduction in striatal MSNs due to a block in their differentiation. Meis2 directly binds to the Zfp503 and Six3 promoters and is required for their expression and specification of D1 and D2 MSNs, respectively. Finally, Meis2 expression is regulated by Dlx1/2 at least partially through the enhancer hs599 in the LGE SVZ. Overall, our findings define a pathway in the LGE whereby Dlx1/2 drives expression of Meis2 which subsequently promotes the fate determination of striatal D1 and D2 MSNs via Zfp503 and Six3.
ACCEPTED MANUSCRIPT
RESEARCH ARTICLE|
14 February 2022
Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum
Zihao Su,
Zihao Su
*
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Ziwu Wang,
Ziwu Wang
*
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Susan Lindtner,
Susan Lindtner
2
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Search for other works by this author on:
Lin Yang,
Lin Yang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Zicong Shang,
Zicong Shang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Yu Tian,
Yu Tian
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Rongliang Guo,
Rongliang Guo
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Yan You,
Yan You
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Wenhao Zhou,
Wenhao Zhou
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
John L. Rubenstein,
John L. Rubenstein
2
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Search for other works by this author on:
Zhengang Yang,
Zhengang Yang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Search for other works by this author on:
Zhuangzhi Zhang
Zhuangzhi Zhang
‡
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
‡Author for correspondence: zz_zhang@fudan.edu.cn
Search for other works by this author on:
Zihao Su
*
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Ziwu Wang
*
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Susan Lindtner
2
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Lin Yang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Zicong Shang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Yu Tian
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Rongliang Guo
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Yan You
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Wenhao Zhou
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
John L. Rubenstein
2
Department of Psychiatry, Nina Ireland Laboratory of Developmental Neurobiology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA
Zhengang Yang
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
Zhuangzhi Zhang
‡
1
Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032
, China
*
These authors contributed equally to this work.
‡Author for correspondence: zz_zhang@fudan.edu.cn
Received:
21 Jul 2021
Accepted:
04 Jan 2022
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Funding Group:
- Award Group:
- Funder(s): National Key Research and Development Program of China
- Award Id(s): 2018YFA0108000
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): National Natural Science Foundation of China
- Award Id(s): 31630032
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): Shanghai Municipal Science and Technology Major Project
- Award Id(s): 2018SHZDZX01
- Funder(s):
Funding Group:
- Award Group:
- Funder(s): National Institute of Mental Health
- Award Id(s): R01 MH049428
- Funder(s):
Development dev.200035.
Article history
Received:
21 Jul 2021
Accepted:
04 Jan 2022
Currently Viewing Accepted Manuscript - Newer Version Available
23 Feb 2022
- Standard view
- Views Icon Views
- Open the PDF for in another window
-
Article Versions Icon
Versions
- Version of Record 23 February 2022
- Accepted Manuscript 14 February 2022
- Share Icon Share
-
Tools Icon
Tools
- Search Site
Citation
Zihao Su, Ziwu Wang, Susan Lindtner, Lin Yang, Zicong Shang, Yu Tian, Rongliang Guo, Yan You, Wenhao Zhou, John L. Rubenstein, Zhengang Yang, Zhuangzhi Zhang; Dlx1/2-dependent expression of Meis2 promotes neuronal fate determination in the mammalian striatum. Development 2022; dev.200035. doi: https://doi.org/10.1242/dev.200035
Download citation file: