Control of neuronal morphology and connectivity: Emerging developmental roles for gap junctional proteins

Baker, Maureen; Macagno, Eduardo R.

doi:10.1016/j.febslet.2014.02.010

Cited by 14 publications

(13 citation statements)

References 146 publications

(220 reference statements)

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“…For example, gap junctions are suggested to function analogously to cell adhesion molecules in mediating cellular recognition and selective neurite adhesion and repulsion 31 . However, these reported adhesive properties are primarily dependent upon the establishment of gap junction structures with the expression of the same connexin in both paired cells 32 .…”

Section: Discussionmentioning

confidence: 99%

Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Shi

Riquelme

et al. 2017

Sci Rep

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Connexins play essential roles in lens homeostasis and development. Here, we identified a new role for Cx50 that mediates cell-cell adhesion function. Cx50 enhanced the adhesive capability of AQP0. Interestingly, the expression of Cx50 alone promoted cell adhesion at a comparable level to AQP0; however, this cell adhesive function was not observed with other lens connexins, Cx43 and Cx46. Moreover, the adhesive property occurred in both homotypic with Cx50 expressed in both pairing cells and heterotypic with Cx50 in only one pairing cell, and this function appears to be unrelated to its role in forming gap junction channels. Cx50 KO lenses exhibited increased intercellular spaces between lens fiber cells. The second extracellular loop domain (E2) is primarily responsible for this adhesive function. Treatment with a fusion protein containing E2 domain inhibited cell adhesion. Furthermore, disruption of cell adhesion by the E2 domains impaired primary lens cell differentiation. Five critical amino acid residues in the E2 domain primarily are involved in cell adhesive function as well as lens epithelial-fiber differentiation. Together, these results suggest that in addition to forming gap junction channels, Cx50 acts as an adhesive molecule that is critical in maintaining lens fiber integrity and epithelial-fiber differentiation.

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Section: Discussionmentioning

confidence: 99%

Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Shi

Riquelme

et al. 2017

Sci Rep

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“…Membrane potential regulation of cell connectivity is a new mechanism in the field. A few pathways have been reported to imply the formation of neural circuit assemblies in vertebrates; Wnt and Semaphorin signaling (Salinas and Zou ; Yoshida ), gap junctional proteins (Baker and Macagno ), and Glycine receptor signaling (Xu and Tian ). We found that GLR production increased when neural V mem was depolarized (Fig.…”

Section: Discussionmentioning

confidence: 99%

Membrane potential depolarization causes alterations in neuron arrangement and connectivity in cocultures

et al. 2014

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BackgroundThe disruption of neuron arrangement is associated with several pathologies. In contrast to action potentials, the role of resting potential (Vmem) in regulating connectivity remains unknown.MethodsNeuron assemblies were quantified when their Vmem was depolarized using ivermectin (Ivm), a drug that opens chloride channels, for 24 h in cocultures with astrocytes. Cell aggregation was analyzed using automated cluster analysis methods. Neural connectivity was quantified based on the identification of isolated somas in phase-contrast images using image processing. Vmem was measured using voltage-sensitive dyes and whole-cell patch clamping. Immunocytochemistry and Western blotting were used to detect changes in the distribution and production of the proteins.ResultsData show that Vmem regulates cortical tissue shape and connectivity. Automated cluster analysis methods revealed that the degree of neural aggregation was significantly increased (0.26 clustering factor vs. 0.21 in controls, P ≤ 0.01). The number of beta-tubulin III positive neural projections was also significantly increased in the neural aggregates in cocultures with Ivm. Hyperpolarized neuron cells formed fewer connections (33% at 24 h, P ≤ 0.05) compared to control cells in 1-day cultures. Glia cell densities increased (33.3%, P ≤ 0.05) under depolarizing conditions.ConclusionVmem can be a useful tool to probe neuronal cells, disease tissues models, and cortical tissue arrangements.

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“…1). The molecular biology and physiology of GJs, as well as their many roles in the nervous system, have recently been expertly reviewed (Sohl and Willecke, 2004;Steyn-Ross et al, 2007;Pereda et al, 2013;Baker and Macagno, 2014). Here, we focus not on the cellular-level signaling mechanics of GJs, but on their role in determining large-scale pattern formation.…”

Section: Introductionmentioning

confidence: 99%

Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form

Mathews

Levin

2016

Developmental Neurobiology

121

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Gap junctions (GJs) are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single-cell functions has long been recognized. However, GJs have another important role: the regulation of large-scale anatomical pattern. GJs are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, GJs underlie the ability of many tissues to implement complex morphogenesis. Here, a review of recent data on patterning roles of GJs in growth of the zebrafish fin, the establishment of left-right patterning, the developmental dysregulation known as cancer, and the control of large-scale head-tail polarity, and head shape in planarian regeneration has been reported. A perspective in which GJs are not only molecular features functioning in single cells, but also enable global neural-like dynamics in non-neural somatic tissues has been proposed. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of GJs to exploit GJ-mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 643-673, 2017.

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Control of neuronal morphology and connectivity: Emerging developmental roles for gap junctional proteins

Cited by 14 publications

References 146 publications

Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Membrane potential depolarization causes alterations in neuron arrangement and connectivity in cocultures

Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form

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