Developmental Genetics, Regeneration, and Evolution of Vertebrate Eye and Retina.
Research SummaryThe Stenkamp lab’s research interests center on the examination of cellular and molecular mechanisms of vertebrate retinal development and regeneration, with a specific focus on photoreceptor differentiation, using zebrafish as the primary experimental model. Specific projects:
Photoreceptor Determination and Differentiation. Vertebrate vision is mediated by the function of rod and cone photoreceptors, and each species generates and maintains characteristic ratios of rods to cones, and of specific cone subtypes with different spectral sensitivities. We are using the zebrafish as a model system for probing the mechanisms that regulate the production and spatial patterns of the different photoreceptor types. The current approaches include transcriptomics, and manipulation of developmental signaling systems that regulate the expression of the cone opsin genes.
Retinal Regeneration. Zebrafish are able to regenerate their retinas after lesions that destroy neurons. Using behavioral assays we have documented the loss and recovery of visual function. This functional recovery takes place despite the presence of histological errors in the regenerated retina. Current studies are focused upon the morphologies of regenerated bipolar neurons, their connections to synaptic partners, and the role of the immune system during the process of regeneration.
Vascular-Neural Interactions. Tissue-tissue interactions are important for the morphogenesis and differentiation of tissues of the vertebrate eye, but roles for the ocular vasculature have been difficult to study due to metabolic functions of the vasculature to supply oxygen and nutrients. In zebrafish embryos, however, the vasculature can be manipulated without causing tissue hypoxia, because diffusion is sufficient for gas and nutrient exchange. We are using temporally-selective manipulations of the vasculature, along with specific zebrafish mutants, to determine components of the vasculature that are required for retinal differentiation.
Evolution in Visually-Challenging Environments. In a multi-institution collaborative project, we are studying the visual systems of threespine stickleback that have recently colonized turbid glacial waters of Iceland.
Predicting Spectral Sensitivity of Visual Pigments using Molecular Simulations. In an interdisciplinary collaborative project, we are developing molecular and statistical models with the capacity to predict the peak spectral sensitivities of teleost cone visual pigments with remarkable accuracy.
Research PublicationsSun C, Galicia C, Stenkamp DL. 2018. Transcripts within rod photoreceptors of the zebrafish retina. BMC Genomics. 19:127.
Patel JS, Brown CJ, Ytreberg FM, Stenkamp DL. 2018. Predicting spectral shift in vertebrate cone visual pigments using atomistic molecular simulations. PLOS Computational Biology.14(1):e1005974.
McGinn TE, Mitchell DM, Meighan PC, Partington N, Leoni D, Jenkins CE, Varnum MD, Stenkamp DL. 2018. Restoration of dendritic complexity, functional connectivity, and diversity of regenerated retinal bipolar neurons. Journal of Neuroscience 38(1):120-136.
Sukeena JM, Galicia CA, Wilson JD, McGinn T, Robison BD, Boughman JW, Postlethwait JH, Braasch I, Stenkamp DL, Fuerst PG. 2016. Characterization and evolution of the spotted gar retina. Journal of Experimental Zoology: Molecular and Developmental Evolution 326(7):403-421.
Dhakal S, Stevens CB, Sebbagh M, Weiss O, Frey RA, Adamson S, Shelden EA, Inbal A, Stenkamp DL. 2015. Abnormal retinal development in cloche mutant zebrafish. Developmental Dynamics 244(11):1439-55.
Mitchell DM, Stevens CB, Frey RA, Hunter SS, Ashino R, Kawamura S, Stenkamp DL. 2015. Retinoic acid signaling regulates expression of the tandemly duplicated long wavelength-sensitive cone opsin genes in zebrafish. PLOS Genetics. 11(8)e1005483.
Sherpa T, Lankford T, McGinn T, Hunter SS, Frey RA, Ryan, M, Sun C, Robison BD, Stenkamp DL. 2014. Retinal regeneration is facilitated by the presence of surviving neurons. Developmental Neurobiology 74(9):851-876.
Kashyap B, Pegorsch L, Frey RA, Sun C, Shelden EA, Stenkamp DL. 2014. Eye-specific gene expression following embryonic ethanol exposure in zebrafish: Roles for heat shock factor 1. Reproductive Toxicology 43C:111-124.