Brain ventricles as windows into brain development and disease

Phan Q Duy¹, Pasko Rakic², Seth L Alper³, William E Butler⁴, Christopher A Walsh⁵, Nenad Sestan², Daniel H Geschwind⁶, Sheng Chih Jin⁷, Kristopher T Kahle⁸

Affiliations

¹ Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
² Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
³ Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴ Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
⁵ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; MGH Hydrocephalus and Neurodevelopmental Disorders Program, Massachusetts General Hospital, Boston, MA, USA. Electronic address: kahle.kristopher@mgh.harvard.edu.

PMID: 34990576
PMCID: PMC9212067
DOI: 10.1016/j.neuron.2021.12.009

Brain ventricles as windows into brain development and disease

Phan Q Duy et al. Neuron. 2022.

. 2022 Jan 5;110(1):12-15.

doi: 10.1016/j.neuron.2021.12.009.

Authors

Phan Q Duy¹, Pasko Rakic², Seth L Alper³, William E Butler⁴, Christopher A Walsh⁵, Nenad Sestan², Daniel H Geschwind⁶, Sheng Chih Jin⁷, Kristopher T Kahle⁸

Affiliations

¹ Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
² Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
³ Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴ Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
⁵ Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁷ Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; MGH Hydrocephalus and Neurodevelopmental Disorders Program, Massachusetts General Hospital, Boston, MA, USA. Electronic address: kahle.kristopher@mgh.harvard.edu.

PMID: 34990576
PMCID: PMC9212067
DOI: 10.1016/j.neuron.2021.12.009

Abstract

Dilation of the fluid-filled cerebral ventricles (ventriculomegaly) characterizes hydrocephalus and is frequently seen in autism and schizophrenia. Recent work suggests that the genomic study of congenital hydrocephalus may be unexpectedly fertile ground for revealing insights into neural stem cell regulation, human cerebrocortical development, and pathogenesis of neuropsychiatric disease.

Keywords: CH; CSF; NSC; brain ventricle; cerebrospinal fluid; congenital hydrocephalus; genomics; neural development; neural stem cell; neurodevelopmental disorders.

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Conflict of interest statement

Declaration of interests D.H.G. and C.A.W. are members of the Neuron advisory board. The other authors declare no competing interests.

Figures

**Figure 1.. Cerebral ventricles as windows into human cerebral cortex development and function**
(A) Brain magnetic resonance imaging (MRI) from a neurologically healthy individual compared to a patient with congenital hydrocephalus and a patient with schizoaffective disorder. Brain MRI of normal adult human brain was obtained from OpenNeuro Dataset ds000221. Original de-identified brain MRI scans were obtained from human patients with hydrocephalus or schizoaffective disorder. (B) Ventriculomegaly as a phenotypic correlate of cortical developmental disorders in humans. Despite the vast heterogeneity among cortical developmental disorders, patients with cerebrocortical disorders often exhibit ventriculomegaly. Thus, ventriculomegaly is potentially a compelling phenotype in a forward genetic screen for novel genetic regulators of human cortical development. In this proposed paradigm, patients diagnosed with ventriculomegaly can be subjected to genetic sequencing to determine potential disease-associated genetic variants. Functional validation of the putative disease genes by study of animal or *in vitro* organoid models may provide new understanding into the genetic regulation of NSCs and human brain development. This knowledge can inform the convergent disease mechanisms shared by cortical developmental disorders to guide investigation of novel therapies.

See this image and copyright information in PMC

References

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Brain ventricles as windows into brain development and disease

Affiliations

Brain ventricles as windows into brain development and disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Grants and funding

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Full Text Sources

Medical