The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling

Zhenjie Zhang; Samuele G. Marro; Yingsha Zhang; Kristin L. Arendt; Christopher Patzke; Bo Zhou; Tyler Fair; Nan Yang; Thomas C. Südhof; Marius Wernig; Lu Chen

doi:10.1126/scitranslmed.aar4338

Research ArticleFragile X Syndrome

The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling

Zhenjie Zhang¹,*,
Samuele G. Marro ²,³,*,
Yingsha Zhang⁴,*,
Kristin L. Arendt¹,
Christopher Patzke⁴,
Bo Zhou⁴,
Tyler Fair²,³,
Nan Yang²,³,
Thomas C. Südhof ⁴,⁵,†,
Marius Wernig ²,³,† and
Lu Chen ¹,†

¹Departments of Neurosurgery, and Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305–5453, USA.
²Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.
³Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.
⁴Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.
⁵Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

↵†Corresponding author. Email: luchen1{at}stanford.edu (L.C.); wernig{at}stanford.edu (M.W.); tcs1{at}stanford.edu (T.C.S.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 01 Aug 2018:
Vol. 10, Issue 452, eaar4338
DOI: 10.1126/scitranslmed.aar4338

Zhenjie Zhang

1Departments of Neurosurgery, and Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305–5453, USA.

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Samuele G. Marro

2Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Yingsha Zhang

4Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Kristin L. Arendt

1Departments of Neurosurgery, and Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305–5453, USA.

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Christopher Patzke

4Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Bo Zhou

4Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Tyler Fair

2Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Nan Yang

2Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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Thomas C. Südhof

4Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

5Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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For correspondence: luchen1@stanford.edu wernig@stanford.edu tcs1@stanford.edu

Marius Wernig

2Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305–5453, USA.

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For correspondence: luchen1@stanford.edu wernig@stanford.edu tcs1@stanford.edu

Lu Chen

1Departments of Neurosurgery, and Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305–5453, USA.

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For correspondence: luchen1@stanford.edu wernig@stanford.edu tcs1@stanford.edu

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Inactivation of the Fmr1 gene that is mutated in fragile X syndrome leads to loss of retinoic acid–mediated homeostatic plasticity in human neurons.

The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling

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