Gap-Junction Proteins in Retinal Development: New Roles for the “Nexus”

Cook, Jeremy E.; Becker, David L.

doi:10.1152/physiol.00007.2009

Cited by 20 publications

(19 citation statements)

References 125 publications

(119 reference statements)

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“…Furthermore, studies suggest the possibility of non-cell-autonomous transfer of miRNAs through microvesicles (Yuan et al, 2009) or gap junctions (Valiunas et al, 2005; Kizana et al, 2009). Indeed, RPCs and many mature retinal cell types are coupled through gap junctions (Bloomfield and Völgyi, 2009; Cook and Becker, 2009). In support of a non-cell-autonomous rescue of the Dicer CKO phenotype, we occasionally observed small areas of recombined (YFP + ) cells that appeared wild type, expressing normal neuronal and RPC markers, which were absent from most Dicer-deficient areas.…”

Section: Discussionmentioning

confidence: 99%

Dicer Is Required for the Transition from Early to Late Progenitor State in the Developing Mouse Retina

Georgi¹,

Reh²

2010

J. Neurosci.

133

146

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MicroRNAs (miRNAs),In an effort to further study the role of miRNAs during retinal development and resolve this apparent conflict, we conditionally knocked out Dicer using a different (␣Pax6cre) line of transgenic mice. In contrast to the previous study, we demonstrate an essential role for miRNAs during mouse retinal development. In the absence of Dicer in the embryonic retina, production of early generated cell types (ganglion and horizontal cells) is increased, and markers of late progenitors are not expressed. This phenotype persists into postnatal retina, in which we find the Dicer-deficient progenitors fail to generate late-born cell types such as rods and Müller glia but continue to generate ganglion cells. We further characterize the dynamic expression of miRNAs during retinal progenitor differentiation and provide a comprehensive profile of miRNAs expressed during retinal development. We conclude that Dicer is necessary for the developmental change in competence of the retinal progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Dicer Is Required for the Transition from Early to Late Progenitor State in the Developing Mouse Retina

Georgi¹,

Reh²

2010

J. Neurosci.

133

146

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“…Gap junction coupling is found throughout the developing nervous system, where it has been postulated to play a number of roles (Cook and Becker, 2009) including regulation of spontaneous firing patterns (Roerig and Feller, 2000; Personius et al, 2007). Here, we explore the role of gap junction coupling in retinal waves, the spontaneous propagating activity generated in the retina prior to the maturation of vision.…”

Section: Introductionmentioning

confidence: 99%

The Role of Neuronal Connexins 36 and 45 in Shaping Spontaneous Firing Patterns in the Developing Retina

Blankenship

Hamby

Firl³

et al. 2011

Journal of Neuroscience

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Gap junction coupling synchronizes activity among neurons in adult neural circuits, but its role in coordinating activity during development is less known. The developing retina exhibits retinal waves - spontaneous depolarizations that propagate among retinal interneurons and drive retinal ganglion cells to fire correlated bursts of action potentials. During development, two connexin isoforms, connexin36 (Cx36) and Cx45, are expressed in bipolar cells and retinal ganglion cells (RGCs), and therefore provide a potential substrate for coordinating network activity. To determine whether gap junctions contribute to retinal waves, we compared spontaneous activity patterns using calcium imaging, whole-cell recording and multielectrode array recording in control, single knockout (ko) mice lacking Cx45 and double knockout (dko) mice lacking both isoforms. Wave frequency, propagation speed and bias in propagation direction were similar in Ctr, Cx36ko, Cx45ko and Cx36/45dko retinas. However, the spontaneous firing rate of individual retinal ganglion cells was elevated in Cx45ko retinas, similar to Cx36ko retinas (Hansen et al., 2005; Torborg and Feller, 2005), a phenotype that was more pronounced in Cx36/45dko retinas. As a result, spatial correlations, as assayed by nearest neighbor correlation and functional connectivity maps, were significantly altered. In addition, Cx36/45dko mice had reduced eye-specific segregation of retinogeniculate afferents. Together, these findings suggest that although Cx36 and Cx45 do not play a role in gross spatial and temporal propagation properties of retinal waves, they strongly modulate the firing pattern of individual RGCs, ensuring strongly correlated firing between nearby RGCs and normal patterning of retinogeniculate projections.

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“…In addition to the circuitry‐related roles attributed in the adult retina (Deans et al, 2002; Feigenspan et al, 2001; Kihara et al, 2006c), Cx‐mediated communication participates in processes underlying its development (for review, see Cook and Becker, 2009), such as apoptosis (Cusato et al, 2003), interkinetic nuclear movement (Pearson et al, 2005b) and propagation of spontaneous activity, also known as “retinal waves” (Roerig and Feller, 2000). In this context, GJ channels have been implicated in the establishment of regulatory compartments during programmed cell death, which helps to establish the distribution of the various cell classes into distinct layers of the retina (Cusato et al, 2003; Linden, 2000).…”

Section: Introductionmentioning

confidence: 99%

Connexin‐mediated communication controls cell proliferation and is essential in retinal histogenesis

Kihara

Santos²,

Osuna-Melo³

et al. 2009

Intl J of Devlp Neuroscience

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Connexin (Cx) channels and hemichannels are involved in essential processes during nervous system development such as apoptosis, propagation of spontaneous activity and interkinetic nuclear movement. In the first part of this study, we extensively characterized Cx gene and protein expression during retinal histogenesis. We observed distinct spatio-temporal patterns among studied Cx and an overriding, ubiquitous presence of Cx45 in progenitor cells. The role of Cx-mediated communication was assessed by using broad-spectrum (carbenoxolone, CBX) and Cx36/Cx50 channel-specific (quinine) blockers. In vivo application of CBX, but not quinine, caused remarkable reduction in retinal thickness, suggesting changes in cell proliferation/apoptosis ratio. Indeed, we observed a decreased number of mitotic cells in CBX-injected retinas, with no significant changes in the expression of PCNA, a marker for cells in proliferative state. Taken together, our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated communication is essential in retinal histogenesis, particularly in the control of cell proliferation.

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Gap-Junction Proteins in Retinal Development: New Roles for the “Nexus”

Cited by 20 publications

References 125 publications

Dicer Is Required for the Transition from Early to Late Progenitor State in the Developing Mouse Retina

Dicer Is Required for the Transition from Early to Late Progenitor State in the Developing Mouse Retina

The Role of Neuronal Connexins 36 and 45 in Shaping Spontaneous Firing Patterns in the Developing Retina

Connexin‐mediated communication controls cell proliferation and is essential in retinal histogenesis

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