About

Jeremy N. Kay is a professor associated with Duke University, specializing in Neurobiology. His research focuses on understanding the neural mechanisms underlying behavior and cognition, contributing to the broader field of neurobiology. His work is recognized within the academic community, and he is involved in mentoring and collaborative research efforts at Duke.

Research topics

• Biology
• Genetics
• Neuroscience
• Cell biology
• Biochemistry
• Anatomy
• Computational biology

Selected publications

• Phosphatidylserine exposure by developing astrocytes initiates microglia-mediated developmental cell death

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-21

  articleOpen accessSenior authorCorresponding

  Developmental cell death is classically attributed to apoptosis, yet in mammalian retina, large numbers of developing astrocytes die non-apoptotically during a defined developmental window. Astrocyte death is important for patterning a cellular template that guides angiogenesis, but the underlying mechanism remains unknown. Here we show that healthy developing astrocytes initiate their own elimination by recruiting microglia via regulated exposure of the membrane lipid phosphatidylserine. Experimentally increasing phosphatidylserine exposure in astrocytes, but not neurons, accelerates their removal by microglia without changing how many astrocytes ultimately survive. This acceleration causes profound vascular defects resembling pathological features of retinopathy of prematurity. Genetic disruption of MFGE8, a phosphatidylserine-binding protein, suppresses microglia-mediated astrocyte killing and prevents vascular pathology despite continued phosphatidylserine exposure. This mechanism extends beyond the retina, because phosphatidylserine also initiates astrocyte death in developing cerebral cortex. Together, these findings identify phosphatidylserine exposure as a developmental signal that times microglia-mediated astrocyte elimination, with essential consequences for neurovascular development.

  PublisherDOI

• Development of Retinal Astroglia

  Annual Review of Vision Science · 2025-07-04 · 3 citations

  reviewOpen access1st authorCorresponding

  Müller cells and retinal nerve fiber layer astrocytes are the major astroglia of the mammalian retina. They have numerous important functions in adulthood for maintaining neuronal homeostasis as well as in developing retina, where they facilitate key events in the assembly of the retinal tissue. Recent years have seen substantial progress in understanding how these astroglial cells develop and how their development shapes the cells around them. We review the mechanisms underlying the formation, maturation, and spatial patterning of Müller glia and retinal astrocytes, with an emphasis on how they acquire their functional properties. We focus on developmental events that have a major impact on overall retinal integrity, such as the formation of neuro-glial junctions at the outer limiting membrane and the patterning of retinal astrocytes into a template that guides angiogenesis. Finally, we discuss examples of retinal diseases that originate in developmental defects affecting Müller cells or retinal astrocytes. These include certain classes of inherited retinal degenerations, as well as retinopathy of prematurity.

  PublisherDOI

• Loss of <scp>MEGF10</scp> Decreases the Number of Perisynaptic Schwann Cells and Innervation of Neuromuscular Junctions in Aging Mice

  Journal of the Peripheral Nervous System · 2025-03-01 · 1 citations

  article

  BACKGROUND AND AIMS: At the neuromuscular junction (NMJ), the synapse between motor neurons and muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate the maintenance and repair of this synapse. While we know how PSC morphology and numbers change in aging and various neuromuscular disorders that adversely affect the NMJ, the molecular mechanisms that alter PSC functions remain unknown. In this study, we investigated whether MEGF10 in PSCs modulates NMJ stability in developing, healthy young adult, middle-aged, and axotomized mice. MEGF10 is a glial phagocytic receptor that is enriched in PSCs compared to other Schwann cells (SCs). METHODS: We isolated PSCs from a transgenic reporter mouse line to assess Megf10 expression at different ages and following nerve injury using qPCR. We then used a conditional mouse lacking Megf10 in all SCs, including PSCs (Megf10 SC-KO mice). We examined NMJs and axonal debris clearance in Megf10 SC-KO mice using confocal microscopy. RESULTS: We found that Megf10 expression in PSCs peaks during development and decreases during aging and following denervation of NMJs. NMJs were morphologically normal in developing and young adult Megf10 SC-KO mice. This was not the case in middle-aged Megf10 SC-KO mice, in which NMJs presented with fewer PSCs, decreased PSC coverage of the endplate, and decreased innervation in comparison to control mice. Following nerve injury-induced damage, axonal debris at the NMJ was cleared faster in Megf10 SC-KO mice; yet, the rate of reinnervation was unchanged compared to control mice. INTERPRETATION: The data in this study suggest that MEGF10 in PSCs functions to maintain PSC number and NMJ innervation during aging. This study also suggests important roles for MEGF10 in mediating the clearance of axonal debris at NMJs following nerve injury.

  PublisherDOI

• Microglia and myeloid cell populations of the developing mouse retina

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-07

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Microglia make important contributions to central nervous system (CNS) development, but the breadth of their distinct developmental functions remain poorly understood. The mouse retina has been a key model system for understanding fundamental mechanisms controlling assembly of the CNS. To gain insight into where and how microglia might influence retinal development, here we identified molecularly unique myeloid cell populations that are selectively present during development, and characterized their anatomical locations. Development-specific transcriptional states were identified using single-cell (sc) and single-nucleus RNA-sequencing (RNA-seq) across multiple timepoints. Transcriptional states were validated in vivo by histological staining for key RNA and/or protein markers. Several of these development-specific myeloid populations have been described before in brain scRNA-seq atlases but not validated in vivo, while others are unique to our retinal dataset. We identify two closely-related microglial populations, labeled by the Spp1 and Hmox1 genes, that are distinguished mainly by activity of the NRF2 transcription factor. Both types are present selectively within the developing retinal nerve fiber layer where they engulf neurons and astrocytes undergoing developmental cell death. Hmox1 + microglia were also localized selectively at the wavefront of developing vasculature during retinal angiogenesis, suggesting that developmental events associated with angiogenesis modulate NRF2 activity and thereby induce microglia to switch between the Spp1 + and Hmox1 + states. Overall, our results identify transcriptional profiles that define specific populations of retinal microglia, opening the way to future investigations of how these programs support microglial functions during development.

  PublisherOA PDFDOI

• Microglia and Myeloid Cell Populations of the Developing Mouse Retina

  Glia · 2025-12-12 · 2 citations

  articleOpen accessSenior authorCorresponding

  ABSTRACT Microglia make important contributions to central nervous system (CNS) development, but the breadth of their distinct developmental functions remains poorly understood. The mouse retina has been a key model system for understanding fundamental mechanisms controlling the assembly of the CNS. To gain insight into where and how microglia might influence retinal development, here we identified molecularly unique myeloid cell populations that are selectively present during development and characterized their anatomical locations. Development‐specific transcriptional states were identified using single‐cell (sc) and single‐nucleus RNA‐sequencing (RNA‐seq) across multiple timepoints. Transcriptional states were validated in vivo by histological staining for key RNA and/or protein markers. Several of these development‐specific myeloid populations have been described before in brain scRNA‐seq atlases but not validated in vivo, while others are unique to our retinal dataset. We identify two closely related microglial populations, labeled by the Spp1 and Hmox1 genes, that are distinguished mainly by transcriptional targets of the NRF2 transcription factor. Both types are present selectively within the developing retinal nerve fiber layer where they engulf neurons and astrocytes undergoing developmental cell death. Hmox1 + microglia were also localized selectively at the wavefront of developing vasculature during retinal angiogenesis, suggesting that developmental events associated with angiogenesis modulate NRF2 activity and thereby induce microglia to switch between the Spp1 + and Hmox1 + states. Overall, our results identify transcriptional profiles that define specific populations of retinal microglia, opening the way to future investigations of how these programs support microglial functions during development.

  PublisherOA PDFDOI

• Cellular and molecular alterations to muscles and neuromuscular synapses in a mouse model of MEGF10-related myopathy

  Skeletal Muscle · 2024-05-17 · 6 citations

  articleOpen access

  Loss-of-function mutations in MEGF10 lead to a rare and understudied neuromuscular disorder known as MEGF10-related myopathy. There are no treatments for the progressive respiratory distress, motor impairment, and structural abnormalities in muscles caused by the loss of MEGF10 function. In this study, we deployed cellular and molecular assays to obtain additional insights about MEGF10-related myopathy in juvenile, young adult, and middle-aged Megf10 knockout (KO) mice. We found fewer muscle fibers in juvenile and adult Megf10 KO mice, supporting published studies that MEGF10 regulates myogenesis by affecting satellite cell differentiation. Interestingly, muscle fibers do not exhibit morphological hallmarks of atrophy in either young adult or middle-aged Megf10 KO mice. We next examined the neuromuscular junction (NMJ), in which MEGF10 has been shown to concentrate postnatally, using light and electron microscopy. We found early and progressive degenerative features at the NMJs of Megf10 KO mice that include increased postsynaptic fragmentation and presynaptic regions not apposed by postsynaptic nicotinic acetylcholine receptors. We also found perisynaptic Schwann cells intruding into the NMJ synaptic cleft. These findings strongly suggest that the NMJ is a site of postnatal pathology in MEGF10-related myopathy. In support of these cellular observations, RNA-seq analysis revealed genes and pathways associated with myogenesis, skeletal muscle health, and NMJ stability dysregulated in Megf10 KO mice compared to wild-type mice. Altogether, these data provide new and valuable cellular and molecular insights into MEGF10-related myopathy.

  PublisherOA PDFDOI

• Generation of an Armcx1 Conditional Knockout Mouse

  genesis · 2024-08-01

  articleOpen access

  ABSTRACT Armadillo repeat‐containing X‐linked protein‐1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo , we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1 fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for β‐actin and Six3 , in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1 fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1‐deficient neurons to degeneration in the setting of additional heritable or environmental stressors.

  PublisherOA PDFDOI

• Retinal neurons establish mosaic patterning by excluding homotypic somata from their dendritic territories

  Cell Reports · 2024-08-01 · 10 citations

  articleOpen accessSenior authorCorresponding

  In vertebrate retina, individual neurons of the same type are distributed regularly across the tissue in a pattern known as a mosaic. Establishment of mosaics during development requires cell-cell repulsion among homotypic neurons, but the mechanisms underlying this repulsion remain unknown. Here, we show that two mouse retinal cell types, OFF and ON starburst amacrine cells, establish mosaic spacing by using their dendritic arbors to repel neighboring homotypic somata. Using transgenic tools and single-cell labeling, we identify a developmental period when starburst somata are contacted by neighboring starburst dendrites; these serve to exclude somata from settling within the neighbor's dendritic territory. Dendrite-soma exclusion is mediated by MEGF10, a cell-surface molecule required for starburst mosaic patterning. Our results implicate dendrite-soma exclusion as a key mechanism underlying starburst mosaic spacing and raise the possibility that this could be a general mechanism for mosaic patterning across many cell types and species.

  PublisherDOI

• Neuroscience: The dynamic development of dendrites

  Current Biology · 2024-09-01

  articleSenior author
  PublisherDOI

• Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling

  Developmental Cell · 2023-08-08 · 11 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Molecular control of neuronal position during retinal development

  NIH · $2.0M · 2014–2019

• Mechanisms of naturally-occurring astrocyte death during retinal development

  NIH · $2.7M · 2019–2027

• Center Core Grant for Vision Research

  NIH · $16.4M · 1997–2026

Frequent coauthors

• Joshua R. Sanes

  Harvard University Press

  11 shared

• Christopher Kozlowski

  Duke University

  10 shared

• Thomas A. Ray

  Duke University

  9 shared

• Jingjing Wang

  9 shared

• Matthew L. O’Sullivan

  7 shared

• Cameron L. Prigge

  Duke University

  6 shared

• Greg D. Field

  5 shared

• Çağla Eroğlu

  Duke University

  5 shared

Labs

• Kay LabPI