Seminar: Fat3 – An Unusual Cadherin Regulating Retinal Lamination and Stratification

Michael D Flyer

Michael Deans, Assistant Professor and Director of Research, Otolaryngology, University of Utah will be delivering a seminar on Fat3 – An Unusual Cadherin Regulating Retinal Lamination and Stratification on Thursday, July 2nd 24th at Noon  in the the Moran Eye Center auditorium.

Abstract: Neurons receive signals through dendrites that vary widely in number and organization, ranging from one primary dendrite to multiple complex dendritic trees. For example, retinal amacrine cells project primary dendrites into discrete strata of the inner plexiform layer and only rarely extend processes into other retinal layers. We have shown that the atypical cadherin Fat3 ensures that ACs develop this unipolar morphology. AC precursors are initially multipolar, but lose neurites as they migrate through the neuroblastic layer. In fat3 mutants, pruning is unreliable and ACs elaborate two dendritic trees: one within the IPL and a second projecting away from the IPL that stratifies to form an additional synaptic layer. More recently we have found that Fat3 is regulated by RNA processing and that one alternatively spliced isoform binds to the Kinesin subunit Kif5b. One exciting hypothesis that we are currently testing is that Kinesin trafficking regulates Fat3 subcellular distribution, thereby mediating Fat3-dependent dendrite formation.

Seminar: Cellular and Molecular Mechanisms of Optic Cup Morphogenesis

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Kristen Kwan, Assistant Professor of Human Genetics, University of Utah will be delivering a seminar on Cellular and Molecular Mechanisms of Optic Cup Morphogenesis on Wednesday, June 24th at Noon  in the the Moran Eye Center auditorium.

Abstract: Developmental defects in eye structure can cause visual impairment in newborns.  These defects often arise very early in eye development, when the basic structure of the eye is generated during optic cup morphogenesis, which transforms the nascent optic vesicle, via a series of complex cell and tissue rearrangements, into the optic cup.  Using zebrafish as our model system and a combination of 4-dimensional live imaging, computational methods, and molecular genetics, we are directly visualizing optic cup morphogenesis and determining underlying mechanisms.  This talk will be focused on our recent work aimed at understanding choroid fissure formation and its disruptions in a particular zebrafish model of ocular coloboma, as well as the role of extracellular matrix proteins and adhesion in driving optic cup formation.

Seminar: Dissecting The Gene Regulatory Network In Retinal Development

Mu flyer

Xiuqian Mu, Assistant Professor of the Department of Ophthalmology from the State University of New York at Buffalo is scheduled to present a seminar at 4pm on Tuesday, September 2, 2014 in the EIHG Auditorium. The title of his seminar is: Dissecting the gene regulatory network in retinal development: One Cut at a time.

The Department of Neurobiology and Anatomy at the University of Utah is hosting.  Faculty host is Monica Vetter.

The Role of NMDA Receptor Activity in Retinal Ganglion Cell Dendrite Development

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This abstract was presented today at the 2014 Association for Research in Vision and Opthalmology (ARVO) meetings in Orlando, Florida by Eerik M. Elias, Ping Wang and Ning Tian.

Full size poster available here.

Purpose: To elucidate mechanisms underlying the dendrite developmental plasticity of retinal ganglion cells, we examined the role of glutamate receptors on retinal ganglion cell dendrite elongation and filopodia elimination.

Methods: We used the JamB genetically labeled subtype of RGCs as our working model. JamB-CreER:YFP ganglion cell dendritic arbors were imaged in whole mount retina using confocal microscopy. Dendrite length, area, branching, and filopodia number were traced and measured using Neurolucida. Visual inputs were blocked by dark-rearing pups after P5. Glutamatergic activity was blocked using daily intraocular injections of AP5 and CNQX from P9 to P13 or genetic ablation of the NMDA receptor in these RGCs.

Results: To test the role of visual inputs on dendrite development, we dark-reared mice from P5 to P30 and found a modest effect on filopodia elimination in JamB RGCs. Anticipating that spontaneous glutamatergic activity in the retina may also contribute to RGC filopodia elimination, we blocked spontaneous glutamatergic activity by daily intraocular injections of AP5 and CNQX from P9 to P13. This led to an increase in filopodia density due to decreased dendrite length but no change in filopodia number. We confirmed this result by examining NMDAR knockout JamB cells (JamB-CreER:YFP:Grin1-/-). As expected, Grin1-/- JamB RGCs have decreased dendrite outgrowth like the pharmacologic blockade. However, filopodia elimination in these cells was significantly decreased as well, suggesting that NMDA and non-NMDA glutamate receptors might regulate the RGC dendritic development in a differential manner. This effect was dramatic at P13. To test if this effect persists into adulthood, we examined Grin1-/- JamB RGCs at P30 and found that they are indistinguishable from wild-type JamB RGCs, suggesting that a compensatory mechanism exists to drive dendrite elongation and filopodia elimination in the absence of the NMDA receptor.

Conclusions: Our study demonstrated that ganglion cell dendrite outgrowth and pruning of filopodia require glutamatergic activity and visual input that act via NMDA and possibly non-NMDA glutamate receptors.

Interesting: Gene Regulator, Onecut1 Important To Retinal Development And Integrity

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This paper, Onecut1 Is Essential for Horizontal Cell Genesis and Retinal Integrity in the Journal of Neuroscience by authors Fuguo Wu, Renzhong Li, Yumiko Umino, Tadeusz J. Kaczynski, Darshan Sapkota, Shengguo Li, Mengqing Xiang, Steven J. Fliesler, David M. Sherry, Maureen Gannon, Eduardo Solessio, and Xiuqian Mu describes the gene regulator Onecut1 as being the key to healthy retinal development and good vision in adulthood.

Essentially, Onecut1 is critical for the formation of horizontal cells, but of fundamental importance to retinal degenerative research, this work implies that horizontal cells might be necessary for the survival of photoreceptor cells.  Of course we have known for some years that horizontal cells are some of the very first cells to respond to retinal degeneration by extensively remodeling, but this is an interesting result that suggests a direct dependence of photoreceptors on the horizontal cells themselves for survival.

Metabolic Differentiation In The Embryonic Retina

Michalis Agathocleous, Nicola K. Love, Owen Randlett, Julia J. Harris, Jinyue Liu, Andrew J. Murray and William A. Harris have published a very interesting story on proliferating cells of the Xenopus laevis retina that documents aerobic glycolysis rather than oxidative phosphorylation.  Historically, this shift in metabolism was termed the Warburg effect where it was originally described in tumorigenesis.  Could it be that this shift in metabolism is more widely used than previously anticipated?  Certainly in the proliferating developing Xenopus laevis retina, it appears so, even in the presence of oxygen.  The only other instance of aerobic glycolosis I am aware of is in T-cells, but that too is associated with oncogenicity.

This really opens up possibilities for metabolic control of a variety of processes in not only development, but also pathology with respect to alternative methods for defining metabolic states and deriving energy.