The Vacuolar-ATPase Complex Regulates Retinoblast Proliferation and Survival, Photoreceptor Morphogenesis, and Pigmentation in the Zebrafish Eye

Nuckels, Richard J.; Ng, Anthony; Darland, Tristan; Gross, Jeffrey M.

doi:10.1167/iovs.08-2743

Cited by 84 publications

(114 citation statements)

References 65 publications

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“…We designed translational blocking and splice-blocking morpholinos to both the Vod1 and V1D subunits of V-ATPase. Injection of embryos with these morpholinos consistently resulted in the hypopigmentation phenotype as reported [28] (Figure 5B), confirming the efficacies of these morpholinos. The heart looping was randomized in the Vod1 morphants ( Figure 5C), consistent with a previous report that inhibition of VATPase by chemical inhibitors induces left-right patterning defects in zebrafish [29].…”

Section: V-atpase Regulates Ciliogenesis In Multiple Organs In Zebrafishsupporting

confidence: 72%

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Chen

et al. 2011

Cell Res

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Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the sorting of various membrane proteins in vitro, but the in vivo functions of them remain largely unknown. We reported previously that SNX10 is a unique member of the SNX family genes in that it has vacuolation activity in cells. We investigate the biological function of SNX10 by loss-of-function assay in this study and demonstrate that SNX10 is required for the formation of primary cilia in cultured cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle and essential for left-right patterning of visceral organs. Mechanistically, SNX10 interacts with V-ATPase complex and targets it to the centrosome where ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo and does so synergistically with SNX10. We further discover that SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. These results identify an SNX10/V-ATPaseregulated vesicular trafficking pathway that is crucial for ciliogenesis, and reveal that SNX10/V-ATPase, through the regulation of cilia formation in various organs, play an essential role during early embryonic development.

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Section: V-atpase Regulates Ciliogenesis In Multiple Organs In Zebrafishsupporting

confidence: 72%

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Chen

et al. 2011

Cell Res

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“…In contrast to the expression pattern of atp6v0c, which has been shown to be expressed in the retinal pigment epithelium and ganglion cells in the eye, the telencephalon, and the pigment cells and mucous cells of the fish body (Wang et al, 2008;Nuckels et al, 2009), atp6v0c2 is expressed specifically in the developing nervous system (Fig. 2).…”

Section: Atp6v0c2 Is Specifically Expressed In the Zebrafish Cnsmentioning

confidence: 90%

“…A recent study reported that apt6v0c mutant zebrafish were microphthalmic, and their eyes possessed a thin, hypopigmented retinal pigmented epithelium (RPE) (Nuckels et al, 2009). BrdU incorporation experiments and TUNEL staining revealed that apt6v0c function was essential for the exit of retinoblasts from the cell cycle, as well as for the sustained proliferation of retinal stem cells (Nuckels et al, 2009).…”

Section: Atp6v0c2 Function Is Dispensable For Neurogenesismentioning

confidence: 99%

“…BrdU incorporation experiments and TUNEL staining revealed that apt6v0c function was essential for the exit of retinoblasts from the cell cycle, as well as for the sustained proliferation of retinal stem cells (Nuckels et al, 2009). In order to determine whether atp6v0c2 has a similar function in neurogenesis during CNS development, we designed an antisense morpholino oligonucleotide (MO) that would interfere with the splicing of apt6v0c2 RNA and generate alternative transcripts that were expected to be nonfunctional (see Supp.…”

Section: Atp6v0c2 Function Is Dispensable For Neurogenesismentioning

confidence: 99%

“…In addition to its role as a V-ATPase subunit, ATP6V0C functions independently to form gap junction complexes and neurotransmitter release channels (Finbow et al, 1995;Morel, 2003). Recent study has shown that mutations in the apt6v0c gene result in defects in retinoblast proliferation and survival in zebrafish, indicating that ATP6V0C plays a critical role during vertebrate eye development and maintenance (Wang et al, 2008;Nuckels et al, 2009). Here we present the specific expression pattern and expected function of atp6v0c2, a second isoform of mammalian atp6v0c, in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

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Neuron‐specific expression of atp6v0c2 in zebrafish CNS

Chung

Kim

et al. 2010

Developmental Dynamics

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*Vacuolar ATPase (V-ATPase) is a multi-subunit enzyme that plays an important role in the acidification of a variety of intracellular compartments. ATP6V0C is subunit c of the V 0 domain that forms the proteolipid pore of the enzyme. In the present study, we investigated the neuron-specific expression of atp6v0c2, a novel isoform of the V-ATPase c-subunit, during the development of the zebrafish CNS. Zebrafish atp6v0c2 was isolated from a genome-wide analysis of the zebrafish mib ta52b mutant designed to identify genes differentially regulated by Notch signaling. Whole-mount in situ hybridization revealed that atp6v0c2 is expressed in a subset of CNS neurons beginning several hours after the emergence of post-mitotic neurons. The ATP6V0C2 protein is co-localized with the presynaptic vesicle marker, SV2, suggesting that it is involved in neurotransmitter storage and/or secretion in neurons. In addition, the loss-of-function experiment suggests that ATP6V0C2 is involved in the control of neuronal excitability. Developmental Dynamics 239:2501-2508,

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The genetics of ocular disorders: Insights from the zebrafish

Morris

2011

Birth Defects Research Pt C

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Proper formation of the vertebrate eye requires a precisely coordinated sequence of morphogenetic events that integrate the developmental contributions of the skin ectoderm, neuroectoderm, and head mesenchyme. Disruptions in this process result in ocular malformations or retinal degeneration and can cause significant visual impairment. The zebrafish is an excellent vertebrate model for the study of eye development and disease due to the transparency of the embryo, its ex utero development, and its amenability to forward genetic screens. This review will present an overview of the genetic methodologies utilized in the zebrafish, a description of several zebrafish models of congenital ocular diseases, and a discussion of the utility of the zebrafish for assessing the pathogenicity of candidate disease alleles.

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The Vacuolar-ATPase Complex Regulates Retinoblast Proliferation and Survival, Photoreceptor Morphogenesis, and Pigmentation in the Zebrafish Eye

Abstract: These results demonstrate that the v-ATPase complex plays several critical roles during vertebrate eye development and maintenance, and they suggest that defects in v-ATPase complex function could possibly underlie human ocular disorders that affect the RPE.

Cited by 84 publications

References 65 publications

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Neuron‐specific expression of atp6v0c2 in zebrafish CNS

The genetics of ocular disorders: Insights from the zebrafish

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