scholarly journals Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization

2019 ◽  
Author(s):  
Steven Hill ◽  
Andrew Blaeser ◽  
Austin A. Coley ◽  
Yajun Xie ◽  
Katherine A. Shepard ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Neuronal Excitability ◽  
Synapse Formation ◽  
Critical Role ◽  
Synaptic Organization ◽  
Cell Type ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Cell Type Specific

Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling between neurons and astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses.

scholarly journals Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Steven A Hill ◽  
Andrew S Blaeser ◽  
Austin A Coley ◽  
Yajun Xie ◽  
Katherine A Shepard ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Neuronal Excitability ◽  
Synapse Formation ◽  
Critical Role ◽  
K Channel ◽  
Synaptic Organization ◽  
Cell Type ◽  
Shh Signaling ◽  
Cell Type Specific

Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses.

scholarly journals Author response: Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization

2019 ◽  
Author(s):  
Steven A Hill ◽  
Andrew S Blaeser ◽  
Austin A Coley ◽  
Yajun Xie ◽  
Katherine A Shepard ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Author Response ◽  
Synaptic Organization ◽  
Cell Type ◽  
Sonic Hedgehog Signaling ◽  
Cell Type Specific

scholarly journals Sonic hedgehog signaling in astrocytes

2020 ◽  
Author(s):  
Steven A. Hill ◽  
Marissa Fu ◽  
A. Denise R. Garcia
Keyword(s):  
Nervous System ◽  
Signaling Pathway ◽  
Functional Properties ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Synapse Formation ◽  
Synaptic Activity ◽  
Molecular Signaling ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling

Abstract Astrocytes are complex cells that perform a broad array of essential functions in the healthy and injured nervous system. The recognition that these cells are integral components of various processes, including synapse formation, modulation of synaptic activity, and response to injury, underscores the need to identify the molecular signaling programs orchestrating these diverse functional properties. Emerging studies have identified the Sonic hedgehog (Shh) signaling pathway as an essential regulator of the molecular identity and functional properties of astrocytes. Well established as a powerful regulator of diverse neurodevelopmental processes in the embryonic nervous system, its functional significance in astrocytes is only beginning to be revealed. Notably, Shh signaling is active only in discrete subpopulations of astrocytes distributed throughout the brain, a feature that has potential to yield novel insights into functional specialization of astrocytes. Here, we discuss Shh signaling and emerging data that point to essential roles for this pleiotropic signaling pathway in regulating various functional properties of astrocytes in the healthy and injured brain.

scholarly journals New Tricks for an Old (Hedge)Hog: Sonic Hedgehog Regulation of Astrocyte Function

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1353
Author(s):  
A. Denise R. Garcia
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Synapse Formation ◽  
Inflammatory Responses ◽  
Molecular Signaling ◽  
Synaptic Organization ◽  
Shh Signaling ◽  
Broad Array ◽  
And Function ◽  
Molecular Signaling Pathway

The Sonic hedgehog (Shh) molecular signaling pathway is well established as a key regulator of neurodevelopment. It regulates diverse cellular behaviors, and its functions vary with respect to cell type, region, and developmental stage, reflecting the incredible pleiotropy of this molecular signaling pathway. Although it is best understood for its roles in development, Shh signaling persists into adulthood and is emerging as an important regulator of astrocyte function. Astrocytes play central roles in a broad array of nervous system functions, including synapse formation and function as well as coordination and orchestration of CNS inflammatory responses in pathological states. Neurons are the source of Shh in the adult, suggesting that Shh signaling mediates neuron–astrocyte communication, a novel role for this multifaceted pathway. Multiple roles for Shh signaling in astrocytes are increasingly being identified, including regulation of astrocyte identity, modulation of synaptic organization, and limitation of inflammation. This review discusses these novel roles for Shh signaling in regulating diverse astrocyte functions in the healthy brain and in pathology.

scholarly journals A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2061-2071 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jingda Xu ◽  
Jin He ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Myeloma Cell ◽  
Sonic Hedgehog Signaling ◽  
Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

scholarly journals A novel role for primary cilia in airway remodeling

2017 ◽  
Vol 313 (2) ◽  
pp. L328-L338 ◽  
Author(s):  
Carol S. Trempus ◽  
Weifeng Song ◽  
Ahmed Lazrak ◽  
Zhihong Yu ◽  
Judy R. Creighton ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Calcium Influx ◽  
Airway Remodeling ◽  
Critical Role ◽  
Calcium Flux ◽  
Airway Smooth Muscle Cells ◽  
Mechanical Stimuli ◽  
Sonic Hedgehog Signaling

Primary cilia (PC) are solitary cellular organelles that play critical roles in development, homeostasis, and disease pathogenesis by modulating key signaling pathways such as Sonic Hedgehog and calcium flux. The antenna-like shape of PC enables them also to facilitate sensing of extracellular and mechanical stimuli into the cell, and a critical role for PC has been described for mesenchymal cells such as chondrocytes. However, nothing is known about the role of PC in airway smooth muscle cells (ASMCs) in the context of airway remodeling. We hypothesized that PC on ASMCs mediate cell contraction and are thus integral in the remodeling process. We found that PC are expressed on ASMCs in asthmatic lungs. Using pharmacological and genetic methods, we demonstrated that PC are necessary for ASMC contraction in a collagen gel three-dimensional model both in the absence of external stimulus and in response to the extracellular component hyaluronan. Mechanistically, we demonstrate that the effect of PC on ASMC contraction is, to a small extent, due to their effect on Sonic Hedgehog signaling and, to a larger extent, due to their effect on calcium influx and membrane depolarization. In conclusion, PC are necessary for the development of airway remodeling by mediating calcium flux and Sonic Hedgehog signaling.

scholarly journals Sonic hedgehog signaling in epithelial tissue development

2019 ◽  
Vol 7 ◽  
pp. 3
Author(s):  
Lu Zheng ◽  
Chen Rui ◽  
Hao Zhang ◽  
Jing Chen ◽  
Xiuzhi Jia ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Gastric Epithelium ◽  
Epithelial Tissue ◽  
Sonic Hedgehog Signaling ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Tissue Repair And Regeneration ◽  
New Treatment

The Sonic hedgehog (SHH) signaling pathway is essential for embryonic development and tissue regeneration. The dysfunction of SHH pathway is involved in a variety of diseases, including cancer, birth defects, and other diseases. Here we reviewed recent studies on main molecules involved in the SHH signaling pathway, specifically focused on their function in epithelial tissue and appendages development, including epidermis, touch dome, hair, sebaceous gland, mammary gland, tooth, nail, gastric epithelium, and intestinal epithelium. The advance in understanding the SHH signaling pathway will give us more clues to the mechanisms of tissue repair and regeneration, as well as the development of new treatment for diseases related to dysregulation of SHH signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document