Connexin 36 Expression Regulates Neuronal Differentiation from Neural Progenitor Cells

Hartfield, Elizabeth M.; Rinaldi, Federica; Glover, Colin P.; Wong, Liang‐Fong; Caldwell, Maeve A.; Uney, James B.

doi:10.1371/journal.pone.0014746

Cited by 49 publications

(47 citation statements)

References 37 publications

(41 reference statements)

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“…In accordance, NPCs lacking Cx43 display reduced levels of P2Y 1 [174] and enhancement in b-catenin transcriptional activity [175], changes that are respectively accompanied by disturbed neuronal migration and increased differentiation. Of note, other Cx species, such as Cx26 and Cx36, may equally be involved in directing developmental neurogenesis [93,176]. Apart from channel-independent actions, HCs are suggested to modulate proliferative activity of NPCs by mediating spontaneous ICW propagation in the radial glial cell population in the VZ.…”

Section: General Concepts Of Connexin and Pannexin Signalingmentioning

confidence: 99%

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Decrock

Bock

Wang

et al. 2015

Cell. Mol. Life Sci.

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The central nervous system (CNS) is composed of a highly heterogeneous population of cells. Dynamic interactions between different compartments (neuronal, glial, and vascular systems) drive CNS function and allow to integrate and process information as well as to respond accordingly. Communication within this functional unit, coined the neuro-glio-vascular unit (NGVU), typically relies on two main mechanisms: direct cell-cell coupling via gap junction channels (GJCs) and paracrine communication via the extracellular compartment, two routes to which channels composed of transmembrane connexin (Cx) or pannexin (Panx) proteins can contribute. Multiple isoforms of both protein families are present in the CNS and each CNS cell type is characterized by a unique Cx/Panx portfolio. Over the last two decades, research has uncovered a multilevel platform via which Cxs and Panxs can influence different cellular functions within a tissue: (1) Cx GJCs enable a direct cell-cell communication of small molecules, (2) Cx hemichannels and Panx channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. In this paper, we discuss current knowledge on their multifaceted contribution to brain development and to specific processes in the NGVU, including synaptic transmission and plasticity, glial signaling, vasomotor control, and blood-brain barrier integrity in the mature CNS. By highlighting both physiological and pathological conditions, it becomes evident that Cxs and Panxs can play a dual role in the CNS and that an accurate fine-tuning of each signaling mechanism is crucial for normal CNS physiology.

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Section: General Concepts Of Connexin and Pannexin Signalingmentioning

confidence: 99%

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Decrock

Bock

Wang

et al. 2015

Cell. Mol. Life Sci.

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“…For example, the connexin disruption of neural progenitors has been shown to reduce neuronal differentiation but increase glial differentiation. 61 Hence, cellular organization of EBs not only affected EB recovery, but also impacted differentiation potential postcryopreservation. Cellular redox state reflected by ROS generation is capable of balancing between self-renewal and differentiation of progenitor cells.…”

Section: The Microenvironment Of Ebs Regulated Cell Recoverymentioning

confidence: 99%

The Microenvironment of Embryoid Bodies Modulated the Commitment to Neural Lineage Postcryopreservation

Sart

Yan

2015

Tissue Engineering Part C: Methods

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Neural progenitor cells are usually derived from pluripotent stem cells (PSCs) through the formation of embryoid bodies (EBs), the three-dimensional (3D) aggregate-like structure mimicking embryonic development. Cryo-banking of EBs is a critical step for sample storage, process monitoring, and preservation of intermediate cell populations during the lengthy differentiation procedure of PSCs. However, the impact of microenvironment (including 3D cell organization and biochemical factors) of EBs on neural lineage commitment postcryopreservation has not been well understood. In this study, intact EBs (I-E) and dissociated EBs (D-E) were compared for the recovery and neural differentiation after cryopreservation. I-E group showed the enhanced viability and recovery upon thaw compared with D-E group due to the preservation of extracellular matrix, cell-cell contacts, and F-actin organization. Moreover, both I-E and D-E groups showed the increased neuronal differentiation and D-E group also showed the enhanced astrocyte differentiation after thaw, probably due to the modulation of cellular redox state indicated by the expression of reactive oxygen species. In addition, mesenchymal stem cell secretome, known to bear a broad spectrum of protective factors, enhanced EB recovery. Taken together, EB microenvironment plays a critical role in the recovery and neural differentiation postcryopreservation.

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“…Cell differentiation is another important step in brain maturation; and, although information is lacking in the neocortex about the involvement of Cxs, experiments in striatal neurospheres have shown that neuronal and oligodendrocyte differentiation is partly mediated by gap junctions (Cx36; Hartfield et al 2011). This demonstrates the involvement of Cxs in all the major steps of cellular maturation.…”

Section: Principles Of Gap Junction Signalingmentioning

confidence: 99%

Gap Junctions in Developing Thalamic and Neocortical Neuronal Networks

Niculescu¹,

Löhmann²

2013

Cerebral Cortex

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The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and developmental regulation. Although interesting findings emerged, showing that different subunits are specifically regulated during development, or that excitatory and inhibitory neuronal networks exhibit various electrical connectivity patterns, gap junctions did not receive much further interest. Originally, it was believed that gap junctions represent simple passageways for electrical and biochemical coordination early in development. Today, we know that gap junction connectivity is tightly regulated, following independent developmental patterns for excitatory and inhibitory networks. Electrical connections are important for many specific functions of neurons, and are, for example, required for the development of neuronal stimulus tuning in the visual system. Here, we integrate the available data on neuronal connectivity and gap junction properties, as well as the most recent findings concerning the functional implications of electrical connections in the developing thalamus and neocortex.

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Connexin 36 Expression Regulates Neuronal Differentiation from Neural Progenitor Cells

Cited by 49 publications

References 37 publications

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

The Microenvironment of Embryoid Bodies Modulated the Commitment to Neural Lineage Postcryopreservation

Gap Junctions in Developing Thalamic and Neocortical Neuronal Networks

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