Biology subjects

Kerstein, P. C.

Publications and source records attributed to Kerstein, P. C..

5 recordsLinked to original sources

bioRxiv2026

Defining cell type-specific diurnal gene expression in the mouse retina

The mammalian retina exhibits daily oscillations in gene expression that contribute to retinal physiology and visual function. However, the extent to which these temporal patterns differ among retinal cell types remains incompletely understood. We performed single-nucleus RNA sequencing in the mouse retina over the day and night, identifying rhythmic genes in the six major retinal cell types. Distinct diurnal gene expression patterns across photoreceptors, interneurons, retinal ganglion cells, and Muller glia correspond to their diverse functions across the light cycle. Even core circadian clock genes exhibited differences in paralog expression and rhythmicity across the retina. In contrast, dopamine signaling via the DRD4 receptor is highly rhythmic across most retinal cell types, suggesting dopamine signaling may be a key rhythmicity cue in the retina under diurnal conditions. This dataset highlights the complexity of daily transcriptional regulation in the retina and provides a resource to explore cell-type-specific diurnal rhythms.

neuroscience↗

bioRxiv2026

Meis2 is required for GABAergic amacrine cell survival in the developing retina.

Amacrine cells (ACs) are the most diverse neuron in the retina, with more than sixty different subtypes, each contributing to the detection of specific visual features. Despite their importance in visual feature detection, the genetic basis for this diversity is still not well understood. Recent single-cell transcriptomic datasets have identified several potential genes that may regulate cellular diversity, but the underlying mechanisms have not been investigated. For example, the transcription factor Meis2 is selectively expressed in the GABAergic subclass of ACs. In this study, we focused on how Meis2 regulates the development of GABAergic ACs. We hypothesized that Meis2 is required for specification and survival of GABAergic ACs. To test this, we used the Meis2 conditional knockout mouse (Meis2-CKO) where Meis2 was deleted from either the entire retina or specifically from AC precursor cells. The deletion of Meis2 led to a ~60% reduction in total GABAergic ACs in the retina. This loss of GABAergic ACs occurred only after postnatal day 5 (P5), suggesting Meis2 is not required for early specification but may be required for survival. To further investigate cell death and survival, we quantified cleaved caspase-3 positive cells in the retina at several developmental timepoints. In Meis2-CKO mice, we found an increase in cleaved caspase-3 immunolabeling at P5 and P6 timepoints coinciding with the reduction of GABAergic ACs. Further analysis of GABAergic AC subtypes demonstrated a subtype-specific cell death in Meis2-CKO retinas. For example, the total number of dopaminergic (TH) ACs were significantly reduced, whereas starburst (ChAT) ACs remained unchanged. These findings suggest that Meis2 is important for the survival of a subset of GABAergic AC subtypes in the mammalian retina. In addition, Meis2 may control the expression of specific survival factors that prevent apoptosis during developmental cell death in the retina.

neuroscience↗

bioRxiv2025

Lead (Pb) exposure results in cell type specific changes in the mouse retina and optic nerve.

Chronic exposure to lead (Pb) is known to cause deficits in neuronal function across the nervous system, including the visual nervous system. Visual deficits have been observed in both humans and rodent models following Pb exposure. However, how Pb exposure causes visual deficits is poorly understood. In this study, we evaluated the effects of Pb toxicity on the retina and optic nerve of the mouse visual nervous system. We used C57BL/6 adult mice of both sexes and divided them into one of three different exposure groups. Adult mice received daily oral gavage of 108mg/kg Na-acetate (control), 54mg/kg Pb-acetate (low dose), or 108mg/kg Pb-acetate (high dose) for 4 weeks. At the end of Pb exposure, whole blood, retina, and optic nerve samples were collected for Pb quantification by atomic absorption spectroscopy and tissue immunohistochemical analyses. Cell type specific markers were used to quantify changes in cell density of retinal ganglion cells (RGCs), oligodendrocytes (OLs), oligodendrocyte precursor cells (OPCs), and myelin structure. Following Pb exposure, we observed a small, but significant reduction in the cell density of RGCs in the retina. However, we found no significant changes in branch thickness or coverage of retinal vasculature following Pb exposure. In the optic nerve after Pb exposure, we found a significant reduction in the cell density of OLs and OPCs. Finally, using immunolabeling for Caspr and Nav1.6, we observed significant structural changes in nodes of Ranvier, suggesting a disruption in myelin structure. Our findings suggested that Pb toxicity may impair survival and maturation process of oligodendrocytes, changes in myelin structures, and potential demyelination of the optic nerve. These results provide the foundation for future investigations into the molecular mechanisms of Pb-dependent changes in myelination and visual nervous system function.

pharmacology and toxicology↗

bioRxiv2023

Gbx2 controls amacrine cell dendrite stratification through Robo1/2 receptors

Within the neuronal classes of the retina, amacrine cells (ACs) exhibit the greatest neuronal diversity in morphology and function. We show that the selective expression of the transcription factor Gbx2 is required for cell fate specification and dendritic stratification of an individual AC subtype in the mouse retina. We identify Robo1 and Robo2 as downstream effectors that when deleted, phenocopy the dendritic misprojections seen in Gbx2 mutants. Slit1 and Slit2, the ligands of Robo receptors, are localized to the OFF layers of the inner plexiform layer where we observe the dendritic misprojections in both Gbx2 and Robo1/2 mutants. We show that Robo receptors also are required for the proper dendritic stratification of additional AC subtypes, such as Vglut3+ ACs. These results show both that Gbx2 functions as a terminal selector in a single AC subtype and identify Slit-Robo signaling as a developmental mechanism for ON-OFF pathway segregation in the retina.

neuroscience↗

bioRxiv2020

Gbx2 identifies two amacrine cell subtypes with distinct molecular, morphological, and physiological properties

Our understanding of how the nervous sytem works is limited by our ability to identify the neuronal subtypes that comprise functional circuits. Using a genetic approach, we show that the transcription factor Gbx2 labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. One subtype of Gbx2+ ACs are likely the previously characterized On-type GABAergic CRH-1 AC. The other Gbx2+ AC population is a previously uncharacterized non-GABAergic, non-Glycinergic (nGnG) AC subtype. Gbx2+ nGnG ACs are On-Off type cells with asymmetric dendritic arbors. Gbx2+ nGnG ACs also exhibit tracer coupling to bipolar cells (BCs) through gap junctions that are modulated by dopamine signaling. This study genetically identifies a previously uncharacterized AC subtype and reveals an unusual AC-BC connectivity through gap junctions that may provide a novel model of synaptic communication and visual circuit function.

neuroscience↗