Severe Retinal Degeneration Associated with Disruption of Semaphorin 4A

Rice, Dennis S.; Huang, Wenhu; Jones, Holly A.; Hansen, Gwenn M.; Ye, Gui-Lan; Xu, Nianha; Wilson, Elizabeth K.; Troughton, K.; Vaddi, Kris; Newton, Robert; Zambrowicz, Brian; Sands, Arthur

doi:10.1167/iovs.04-0020

Cited by 47 publications

(38 citation statements)

References 39 publications

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“…It is therefore possible that Sema4A also promotes growth cone collapse of cultured hippocampal neurons by stimulating R-Ras GAP activities through B-type plexins. Recent studies investigating the roles of semaphorins revealed not only the crucial involvements of each semaphorin in axon guidance but also in the ligand-receptor interactions between semaphorins and plexins essential for neural development (21)(22)(23)(24)(25). Plexin-B2 is not only a crucial component of neural tube development but also a key molecule that directs proliferation and migration of granule cell precursors in the developing dentate gyrus, olfactory bulb, and cerebellum (21).…”

Section: Discussionmentioning

confidence: 99%

“…This raises the possibility that many semaphorins including Sema4D and Sema4A function in concert to regulate the migration of GnRH-1 cells in vivo. Analysis of Sema4A-deficient mice revealed the non-redundant roles of Sema4A in the developmental path of retinal photoreceptor cells, although the receptors involved have not yet been clarified (25). For these reasons, Sema4A may play a crucial role in the development of the neural system through the interaction with B-type plexins in concert with other semaphorin members.…”

Section: Discussionmentioning

confidence: 99%

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Sema4A induces cell morphological changes through B-type plexin-mediated signaling

Yukawa

Tanaka²,

Yoshida³

et al. 2009

Int J Mol Med

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Abstract. Semaphorins are a family of secreted and membranebound proteins known as axonal pathfinders. Sema4A, a member of class 4 semaphorins, induces growth cone collapse of hippocampal neurons. The binding of Sema4A to growth cones indicates the presence of receptors transmitting signals through the intracellular effectors to induce growth cone collapse in hippocampal neurons. Transfection experiments of the candidate receptor genes into COS-7 cells demonstrated that Sema4A binds to axonal guidance receptors Plexin-B1, -B2 and -B3. To identify the functional Sema4A receptor and the signal transduction machinery, COS-7 cell contraction assay was performed, in which intracellular signal transmission induced by Sema4A triggered cell contraction. Expression vectors encoding plexins and Rnd1, a Rho family GTPase, were transfected into COS-7 cells, and a proportion of contracted cells among the transfectants was determined after incubation with Sema4A. The results demonstrated that the combination of Rnd1 and Plexin-B1, -B2 or -B3 induced significant cell contraction, indicating that B-type plexins transmit an intracellular signal of Sema4A through Rnd1. To further study the mechanism of B-type plexin-mediated signaling in Sema4A-induced growth cone collapse, mouse hippocampal neurons transfected with a control or expression plasmid encoding a constitutively active mutant of R-Ras (R-RasQL) were stimulated with Sema4A, followed by the assessment of growth cone collapse. Expression of R-RasQL significantly blocked Sema4A-induced growth cone collapse in the hippocampal neurons compared with the control plasmid. Sema4A thus induces growth cone collapse through the down-regulation of R-Ras activity in mouse hippocampal neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sema4A induces cell morphological changes through B-type plexin-mediated signaling

Yukawa

Tanaka²,

Yoshida³

et al. 2009

Int J Mol Med

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“…In the P10 cornea we detected expression of Sema4a and Nrp1, encoding semaphorin 4A and neuropilin, respectively. Semaphorin 4A has been studied in the retina (Rice et al 2004) with no prior reports of its presence in the cornea. Semaphorin 3A and its receptor neuropilin have been reported to play a role in the initial formation of a nerve ring surrounding the cornea (Lwigale and Bronner-Fraser 2007).…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon

Lee

Schumacher

et al. 2008

Experimental Eye Research

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The cornea continues to mature after birth to develop a fully functional, refractive and protective barrier tissue. Here we investigated the complex biological events underlying this process by profiling global genome-wide gene expression patterns of the immature postnatal day 10 and seven week-old adult mouse cornea. The lens and tendon were included in the study to increase the specificity of genes identified as up regulated in the corneal samples. Notable similarities in gene expression between the cornea and the tendon were in the mesenchymal extracellular matrix collagen (types I, III, V, VI) and proteoglycan (lumican, decorin and biglycan) genes. Expression similarities in the cornea and lens were limited to certain epithelial genes and the crystallins. Approximately 76 genes were over expressed in the cornea samples that showed basal expression levels in the lens and tendon. Thirty-two of these were novel with no known functions in the cornea. These include genes with a potential role in protection against oxidative stress (Dhcr24, Cdo1, Akr1b7, Prdx6), inflammation (Ltb4dh, Wdr1), ion-transport (Pdzk1ip1, Slc12a2, Slc25a17) and transcription (Zfp36l3, Pdzk1ip1). Direct comparison of the cornea of two ages showed selective up regulation of 50 and 12 genes in the P10 and adult cornea, respectively. Of the up regulated P10 genes several encode extracellular matrix collagens and proteoglycans that are stable components of the adult cornea and their high transcriptional activity at P10 indicate a period of active corneal growth and matrix deposition in the young cornea. Much less is known about the genes selectively over expressed in the adult cornea; some relate to immune response and innervation (Npy), and possibly to electron transport (Cyp24a1, Cyp2f2) and others of yet unknown functions in the cornea (Rgs10, Psmb8, Xlr4)). This study detected expression of genes with known functions in the cornea, providing additional validation of the microarray experiments. Importantly, it identified several novel genes whose functions have not been investigated in the cornea.

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“…Most genes associated with autosomal dominant forms of RP are expressed specifically in rod photoreceptors, including genes associated with phototransduction (RHO, GUCA1B) (33,34), photoreceptor-specific transcription factors (CRX, NRL) (35,36), or structural characteristics specific to photoreceptors (RDS, RP1) (37)(38)(39)(40). Other autosomal dominant RP genes are expressed in heterogeneous tissues including the retina and/or the retinal pigment epithelium, such as pre-mRNA splicing factors PRPF3, PRPF8, and PRPF31 (41-43) and the transmembrane protein SEMA4A (44). RP17 is associated with the R14W missense mutation in the signal sequence of CA4 (11).…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

Ogilvie¹,

Ohlemiller

Shah

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Members of the carbonic anhydrase (CA) family play an important role in the regulation of pH, CO 2 , ion, and water transport. CA IV and CA XIV are membrane-bound isozymes expressed in the eye. CA IV immunostaining is limited to the choriocapillaris overlying the retina, whereas CA XIV is expressed within the retina in Müller glial cells and retinal pigment epithelium. Here, we have characterized the physiological and morphological phenotype of the CA IV-null, CA XIV-null, and CA IV/CA XIV-double-null mouse retinas. Flash electroretinograms performed at 2, 7, and 10 months of age showed that the rod/cone a-wave, b-wave, and cone b-wave were significantly reduced (26–45%) in the CA XIV-null mice compared with wild-type littermates. Reductions in the dark-adapted response were not progressive between 2 and 10 months, and no differences in retinal morphology were observed between wild-type and CA XIV-null mice. Müller cells and rod bipolar cells had a normal appearance. Retinas of CA IV-null mice showed no functional or morphological differences compared with normal littermates. However, CA IV/CA XIV double mutants showed a greater deficit in light response than the CA XIV-null retina. Our results indicate that CA XIV, which regulates extracellular pH and pCO 2 , plays an important part in producing a normal retinal light response. A larger functional deficit in the CA IV/CA XIV double mutants suggests that CA IV can also contribute to pH regulation, at least in the absence of CA XIV.

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Severe Retinal Degeneration Associated with Disruption of Semaphorin 4A

Abstract: These findings identify a previously unknown function of Sema4A in the developing visual system and provide a useful model for understanding cell-cell interactions that occur between photoreceptors and the RPE.

Cited by 47 publications

References 39 publications

Sema4A induces cell morphological changes through B-type plexin-mediated signaling

Sema4A induces cell morphological changes through B-type plexin-mediated signaling

Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

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