---
_id: '9793'
abstract:
- lang: eng
  text: Astrocytes extensively infiltrate the neuropil to regulate critical aspects
    of synaptic development and function. This process is regulated by transcellular
    interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes
    coordinate developmental processes among one another to parse out the synaptic
    neuropil and form non-overlapping territories is unknown. Here we identify a molecular
    mechanism regulating astrocyte-astrocyte interactions during development to coordinate
    astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked,
    astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for
    territory and morphological complexity in the developing mouse cortex. Furthermore,
    conditional deletion of Hepacam from developing astrocytes significantly impairs
    gap junction coupling between astrocytes and disrupts the balance between synaptic
    excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy
    with subcortical cysts in humans. Therefore, our findings suggest that disruption
    of astrocyte self-organization mechanisms could be an underlying cause of neural
    pathology.
acknowledgement: This work was supported by the National Institutes of Health (R01
  DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice
  Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships
  from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer
  lab was supported by the European Research Council (ERC) under the European Union’s
  Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported
  by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke
  Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte
  for assistance with proteomic experiments, and Dr. D. Silver for critical review
  of the manuscript. Cartoon elements of figure panels were created using BioRender.com.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine T.
  full_name: Baldwin, Katherine T.
  last_name: Baldwin
- first_name: Christabel X.
  full_name: Tan, Christabel X.
  last_name: Tan
- first_name: Samuel T.
  full_name: Strader, Samuel T.
  last_name: Strader
- first_name: Changyu
  full_name: Jiang, Changyu
  last_name: Jiang
- first_name: Justin T.
  full_name: Savage, Justin T.
  last_name: Savage
- first_name: Xabier
  full_name: Elorza-Vidal, Xabier
  last_name: Elorza-Vidal
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Raúl
  full_name: Estévez, Raúl
  last_name: Estévez
- first_name: Ru-Rong
  full_name: Ji, Ru-Rong
  last_name: Ji
- first_name: Cagla
  full_name: Eroglu, Cagla
  last_name: Eroglu
citation:
  ama: Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization
    and coupling. <i>Neuron</i>. 2021;109(15):2427-2442.e10. doi:<a href="https://doi.org/10.1016/j.neuron.2021.05.025">10.1016/j.neuron.2021.05.025</a>
  apa: Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal,
    X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling.
    <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2021.05.025">https://doi.org/10.1016/j.neuron.2021.05.025</a>
  chicago: Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang,
    Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls
    Astrocyte Self-Organization and Coupling.” <i>Neuron</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.neuron.2021.05.025">https://doi.org/10.1016/j.neuron.2021.05.025</a>.
  ieee: K. T. Baldwin <i>et al.</i>, “HepaCAM controls astrocyte self-organization
    and coupling,” <i>Neuron</i>, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.
  ista: Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras
    X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls
    astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.
  mla: Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization
    and Coupling.” <i>Neuron</i>, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10,
    doi:<a href="https://doi.org/10.1016/j.neuron.2021.05.025">10.1016/j.neuron.2021.05.025</a>.
  short: K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal,
    X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron
    109 (2021) 2427–2442.e10.
date_created: 2021-08-06T09:08:25Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2026-06-18T19:57:22Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2021.05.025
ec_funded: 1
external_id:
  isi:
  - '000692851900010'
  pmid:
  - '34171291'
intvolume: '       109'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.neuron.2021.05.025
month: '08'
oa: 1
oa_version: Published Version
page: 2427-2442.e10
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
  eissn:
  - 1097-4199
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: HepaCAM controls astrocyte self-organization and coupling
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...