Biology subjects

Bills, J. D.

Publications and source records attributed to Bills, J. D..

3 recordsLinked to original sources

bioRxiv2024

Retinal neuroanatomy of two emerging model organisms, the spiny mouse (Acomys dimidiatus) and the Mongolian gerbil (Meriones unguiculatus)

PurposeDegenerative eye diseases such as macular degeneration and retinitis pigmentosa slowly deteriorate vision, ultimately leading to blindness. Current research with laboratory animal models largely utilizes small mammals that are nocturnal and lack the ability to restore lost vision. In contrast, the Mongolian gerbil is a diurnal rodent with good photopic vision, and the eastern spiny mouse is a small desert-dwelling rodent with remarkable regenerative capabilities. The goal of this study was to identify several antibodies that detect retinal cell classes in Meriones and Acomys, and to describe the retinal anatomy of these two species in comparison to outbred laboratory mice (Mus musculus). MethodsRetinal sections were obtained from adult eyes and subjected to histological or immuno-staining with antibodies for various retinal cell types. Sections were imaged by light, fluorescence, and confocal microscopy, assessing cell number and morphology. Cell density, morphology, and placement were compared between species qualitatively and quantitatively. ResultsImmunohistochemical visualization and analysis of all general classes of retinal neurons and Muller glia revealed a classic assembly of retinal cells with a few deviations compared to Mus. Meriones displayed the highest density of cone photoreceptors and Acomys the lowest. A higher density of bipolar cell bodies in the proximal portion of the inner nuclear layer was observed in both Acomys and Meriones compared to Mus, and both species exhibited an increase in amacrine cell density compared to Mus. ConclusionWe have characterized similarities and differences in the retinal anatomy and cellular density between Meriones, Acomys, and Mus. We identified several commercially available antibodies that reliably detect retinal cell types in the Acomys and Meriones retina. Our results provide a foundation for future research into the visual system adaptations of both of these interesting rodent species.

cell biology↗

bioRxiv2022

Chromatin remodeler Chd7 regulates photoreceptor development and outer segment length

Mutations in the chromatin remodeling factor CHD7 are the predominant cause of CHARGE syndrome, a congenital disorder that frequently includes ocular coloboma. Although CHD7 is known to be required for proper ocular morphogenesis, its role in retinal development has not been thoroughly investigated. Given that individuals with CHARGE syndrome can experience visual impairment even in the absence of coloboma, a better understanding of CHD7 function in the retina is needed. In this study, we characterized the expression pattern of Chd7 in the developing zebrafish and mouse retina and documented ocular and retinal phenotypes in Chd7 loss-of-function mutants. Zebrafish Chd7 was expressed throughout the retinal neuroepithelium when retinal progenitor cells were actively proliferating, and later in subsets of newly post-mitotic retinal cells. At stages of retinal development when most retinal cell types had terminally differentiated, Chd7 expression remained strong in the ganglion cell layer and in some cells in the inner nuclear layer. Intriguingly, strong expression of Chd7 was also observed in the outer nuclear layer where it was co-expressed with markers of post-mitotic cone and rod photoreceptors. Expression of mouse CHD7 displayed a similar pattern, including expression in the ganglion cells, subsets of inner nuclear layer cells, and in the distal outer nuclear layer as late as P15. Two different mutant chd7 zebrafish lines were characterized for ocular and retinal defects. These mutants displayed microphthalmia, reduced numbers of cone photoreceptors, and truncated rod and cone photoreceptor outer segments. Reduced cone photoreceptor number and abnormal outer segments were also observed in heterozygous Chd7 mutant mice. Taken together, our results in zebrafish and mouse reveal a conserved, previously undescribed role for Chd7 in retinal development and photoreceptor outer segment morphogenesis. Moreover, our work suggests an avenue of future investigation into the pathogenesis of visual system defects in CHARGE syndrome. HighlightsO_LIChd7 is expressed in both retinal progenitor cells and in differentiated retinal neurons, including post-mitotic rod and cone photoreceptors. C_LIO_LILoss of Chd7 results in a significant decrease in cone photoreceptors in both zebrafish and mouse. C_LIO_LICone and rod photoreceptor outer segments are truncated in chd7 mutants, suggesting a heretofore unappreciated role for Chd7 in outer segment morphogenesis. C_LI

developmental biology↗

bioRxiv2019

Her9/HES4 is required for retinal photoreceptor development, maintenance, and survival

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange (bHLH-O) transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormally truncated outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Muller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival.

developmental biology↗