HepaCAM controls astrocyte self-organization and coupling

Baldwin, Katherine T.; Tan, Christabel Xin; Strader, Samuel; Jiang, Changyu; Savage, Justin T; Elorza‐Vidal, Xabier; Contreras, Ximena; Rülicke, Thomas; Hippenmeyer, Simon; Estévez, Raúl; Ji, Ru-Rong; Eroğlu, Çağla

doi:10.1016/j.neuron.2021.05.025

Cited by 76 publications

(94 citation statements)

References 62 publications

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“…wildtype astrocytes, suggesting that HepaCAM controls territory competition (Baldwin et al, 2021). Interestingly, this study demonstrated that HepaCAM affects the localization and stabilization of Cx43, which is important for proper astrocyte morphology independent of its channel activity (Baldwin et al, 2021).…”

Section: Astrocyte Territory Determinationmentioning

confidence: 73%

“…Astrocytes may use these networks to coordinate neuronal activity, making their selectivity and relationship to astrocyte domains even more intriguing. However, the extent to which the connections between astrocytes affect tiling is currently unknown, though Cx43 is important for astrocyte morphology, which could be an important contributor to tiling (Baldwin et al, 2021 ).…”

Section: Introduction To Astrocyte Tilingmentioning

confidence: 99%

“…Recently, a new study described the astrocyte-enriched Hepatocyte Cell Adhesion Molecule HepaCAM (or GlialCAM) in astrocyte development and tiling. Using loss-of-function studies, this work demonstrated that Hepacam mutants had smaller territory volume during development, both in vitro and in vivo (Baldwin et al, 2021 ). Mosaic Hepacam conditional knockouts showed that wildtype astrocytes overlapped significantly more with knockout astrocytes than with other wildtype astrocytes, suggesting that HepaCAM controls territory competition (Baldwin et al, 2021 ).…”

Section: Introduction To Astrocyte Tilingmentioning

confidence: 99%

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Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

Barber

Ali

Kucenas

2022

Front. Cell. Neurosci.

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Tiling is a developmental process where cell populations become evenly distributed throughout a tissue. In this review, we discuss the developmental cellular tiling behaviors of the two major glial populations in the central nervous system (CNS)—oligodendrocyte progenitor cells (OPCs) and astrocytes. First, we discuss OPC tiling in the spinal cord, which is comprised of the three cellular behaviors of migration, proliferation, and contact-mediated repulsion (CMR). These cellular behaviors occur simultaneously during OPC development and converge to produce the emergent behavior of tiling which results in OPCs being evenly dispersed and occupying non-overlapping domains throughout the CNS. We next discuss astrocyte tiling in the cortex and hippocampus, where astrocytes migrate, proliferate, then ultimately determine their exclusive domains by gradual removal of overlap rather than sustained CMR. This results in domains that slightly overlap, allowing for both exclusive control of “synaptic islands” and astrocyte-astrocyte communication. We finally discuss the similarities and differences in the tiling behaviors of these glial populations and what remains unknown regarding glial tiling and how perturbations to this process may impact injury and disease.

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Section: Astrocyte Territory Determinationmentioning

confidence: 73%

Section: Introduction To Astrocyte Tilingmentioning

confidence: 99%

Section: Introduction To Astrocyte Tilingmentioning

confidence: 99%

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Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

Barber

Ali

Kucenas

2022

Front. Cell. Neurosci.

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“…Human astrocytes were cultured for 5-6 days in 10% FBS containing DMEM medium, trypsinized, counted, and resuspended in serum-free neuronal growth medium and plated on DIV6-8 cortical neuronal cultures maintained in serum-free neuronal growth medium at a neuron to astrocyte ratio of 3:1 which is similar to the ratio found in human brain cortex (Herculano-Houzel, 2014) and as used by others (Baldwin et al, 2021;. Twelve to sixteen hours later, cocultures were treated with S1P (100 nM) for the indicated times.…”

Section: Coculture Of Human Astrocytes With Mouse Cortical Neurons and S1p Stimulationmentioning

confidence: 99%

Neuronal contact upregulates astrocytic sphingosine‐1‐phosphate receptor 1 to coordinate astrocyte‐neuron cross communication

Singh

Kordula

Spiegel

2021

Glia

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Astrocytes, the most abundant glial cells in the mammalian brain, directly associate with and regulate neuronal processes and synapses and are important regulators of brain development. Yet little is known of the molecular mechanisms that control the establishment of astrocyte morphology and the bi-directional communication between astrocytes and neurons. Here we show that neuronal contact stimulates expression of S1PR1, the receptor for the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), on perisynaptic astrocyte processes and that S1PR1 drives astrocyte morphological complexity and morphogenesis. Moreover, the S1P/S1PR1 axis increases neuronal contact-induced expression of astrocyte secreted synaptogenic factors SPARCL1 and thrombospondin 4 that are involved in neural circuit assembly. Our findings have uncovered new functions for astrocytic S1PR1 signaling in regulation of bi-directional astrocyte-neuron crosstalk at the nexus of astrocyte morphogenesis and synaptogenesis.

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“…Despite progress on the cues that drive neuronal tiling, much less is known about the molecular signaling that ensures glial tiling. Recently, hepatocyte cell adhesion molecule (hepaCAM) has been shown to be required form non-overlapping territories of astrocytes in the mouse brain (Baldwin et al, 2021). hepaCAM is enriched in astrocytes and controls the competition for astrocyte territory in the developing mouse cortex.…”

Section: Molecular Signals That Mediate Tilingmentioning

confidence: 99%

Tetris in the Nervous System: What Principles of Neuronal Tiling Can Tell Us About How Glia Play the Game

DeSantis

Smith

2021

Front. Cell. Neurosci.

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The precise organization and arrangement of neural cells is essential for nervous system functionality. Cellular tiling is an evolutionarily conserved phenomenon that organizes neural cells, ensuring non-redundant coverage of receptive fields in the nervous system. First recorded in the drawings of Ramon y Cajal more than a century ago, we now have extensive knowledge of the biochemical and molecular mechanisms that mediate tiling of neurons. The advent of live imaging techniques in both invertebrate and vertebrate model organisms has enhanced our understanding of these processes. Despite advancements in our understanding of neuronal tiling, we know relatively little about how glia, an essential non-neuronal component of the nervous system, tile and contribute to the overall spatial arrangement of the nervous system. Here, we discuss lessons learned from neurons and apply them to potential mechanisms that glial cells may use to tile, including cell diversity, contact-dependent repulsion, and chemical signaling. We also discuss open questions in the field of tiling and what new technologies need to be developed in order to better understand glial tiling.

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HepaCAM controls astrocyte self-organization and coupling

Cited by 76 publications

References 62 publications

Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

Neuronal contact upregulates astrocytic sphingosine‐1‐phosphate receptor 1 to coordinate astrocyte‐neuron cross communication

Tetris in the Nervous System: What Principles of Neuronal Tiling Can Tell Us About How Glia Play the Game

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