About

Michel Bagnat is the Nanaline Duke Distinguished Professor of Cell Biology at Duke University School of Medicine. He is a member of the Duke Cancer Institute and an affiliate of the Duke Regeneration Center. His primary research focuses on cell and molecular biology, with involvement in the Program in Cell and Molecular Biology, Developmental & Stem Cell Biology Program, and the University Program in Genetics and Genomics. His work contributes to understanding fundamental biological processes, particularly in the context of development and disease.

Research topics

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

Selected publications

• Rediscovering the rete ovarii, a secreting auxiliary structure to the ovary

  eLife · 2025-03-19 · 3 citations

  articleOpen access

  The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the mouse ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow toward the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherDOI

• Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome

  UNC Libraries · 2025-04-02

  articleOpen access

  Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome-rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene-assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to an increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.

  PublisherDOI

• Pro-ferroptotic lipids as key control points for caveola formation and disassembly

  Cell Reports · 2025-06-01 · 9 citations

  articleOpen access

  Caveolae are specialized plasma membrane domains with a unique lipid composition. Lipid peroxidation has recently been implicated in triggering caveola disassembly, releasing cavin proteins to regulate oxidative-stress-associated cellular processes, particularly ferroptosis. Here, we investigated how specific lipids influence caveola formation and their response to oxidative stress. A targeted screening of pro-ferroptotic enzymes identified ACSL4, a key enzyme in synthesizing polyunsaturated fatty acid (PUFA)-linked phospholipids, and ether phospholipid biosynthesis enzymes as critical regulators of caveola formation. Membrane-incorporated omega-6 PUFAs promoted caveola formation, while their displacement by omega-3 PUFAs or monounsaturated fatty acids disrupted this process. Importantly, oxidation of omega-6 PUFA chains in phosphatidylethanolamine (PE) triggered caveola disassembly during lipid peroxidation, potentially by affecting cavin-membrane interactions. These findings unveil a new model for caveola formation and signaling, linking caveola dynamics to ferroptosis with pro-ferroptotic lipids as essential caveolar components and key control points for caveola disassembly under oxidative stress.

  PublisherOA PDFDOI

• Author response: Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

  2025-02-12

  peer-reviewOpen access

  The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherDOI

• Author response: Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome

  2025-02-10

  peer-reviewOpen accessSenior author

  Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.

  PublisherDOI

• A self-limiting mechanotransduction feedback loop ensures robust organ formation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-25

  preprintOpen access

  Abstract Organ morphogenesis uses mechanotransduction feedback loops to convert forces into gene expression changes that regulate cell mechanics. How these loops integrate with developmental programs to ensure robust outcomes remains unclear. We show Yap mechanotransduction establishes a self-limiting positive feedback loop for semicircular canal formation in zebrafish. Canal development proceeds through bud initiation, extension, and fusion within the otic epithelium. Local swelling of hyaluronan-rich extracellular matrix (ECM) in the bud activates Yap in a spatial pattern. Yap induces its target ccn1l1 , promoting further ECM expansion to sustain bud extension. This feedback loop confers developmental robustness: graded knockdown of ccn1l1 reduces extension rate, yet canal formation persists and fails only with strong disruption. Critically, the loop contains its own termination mechanism. During bud fusion, PKA-CREB signaling, activated by an adhesion GPCR, gpr126, suppresses ccn1l1 , ending the loop. These findings reveal how mechanotransduction loops with built-in termination provide developmental control by integrating mechanical forces, transcriptional responses, and morphogenetic outcomes.

  PublisherOA PDFDOI

• Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome

  eLife · 2025-02-10 · 2 citations

  preprintOpen accessSenior author

  Abstract Dietary protein absorption in neonatal mammals and fishes relies on the function of a specialized and conserved population of highly absorptive lysosome rich enterocytes (LREs). The gut microbiome has been shown to enhance absorption of nutrients, such as lipids, by intestinal epithelial cells. However, whether protein absorption is also affected by the gut microbiome is poorly understood. Here, we investigate connections between protein absorption and microbes in the zebrafish gut. Using live microscopy-based quantitative assays, we find that microbes slow the pace of protein uptake and degradation in LREs. While microbes do not affect the number of absorbing LRE cells, microbes lower the expression of endocytic and protein digestion machinery in LREs. Using transgene assisted cell isolation and single cell RNA-sequencing, we characterize all intestinal cells that take up dietary protein. We find that microbes affect expression of bacteria-sensing and metabolic pathways in LREs, and that some secretory cell types also take up protein and share components of protein uptake and digestion machinery with LREs. Using custom-formulated diets, we investigated the influence of diet and LRE activity on the gut microbiome. Impaired protein uptake activity in LREs, along with a protein-deficient diet, alters the microbial community and leads to increased abundance of bacterial genera that have the capacity to reduce protein uptake in LREs. Together, these results reveal that diet-dependent reciprocal interactions between LREs and the gut microbiome regulate protein absorption.

  PublisherDOI

• Tissue-wide, synchronous Erk oscillations time the segmentation of the zebrafish notochord

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-02 · 1 citations

  preprintOpen access

  The generation of a periodic body plan is a fundamental property of vertebrates. While biological oscillators provide a mechanism for timing the formation of repeated structures, few examples of signaling oscillators have been identified in development. Here, we show that the addition of repeating mineralizing segments in the zebrafish notochord is timed by tissue-wide, synchronous oscillations of Erk activity. The oscillations are mediated by delayed negative feedback from spry and dusp and expression of the Egf ligand. The uniform increase in egf expression controls the emergence of the oscillations, revealing the mechanism controlling the onset of notochord segmentation. Together, our work reveals an instance of synchronous clocks timing a patterning process and controlling the development of the vertebral column from the notochord.

  PublisherOA PDFDOI

• Author response: Protein absorption in the zebrafish gut is regulated by interactions between lysosome rich enterocytes and the microbiome

  2025-03-13

  peer-reviewOpen accessSenior author
  PublisherDOI

• Rediscovering the Rete Ovarii: a secreting auxiliary structure to the ovary

  eLife · 2025-02-12 · 1 citations

  preprintOpen access

  Abstract The rete ovarii (RO) is an appendage of the ovary that has been given little attention. Although the RO appears in drawings of the ovary in early versions of Gray’s Anatomy, it disappeared from recent textbooks, and is often dismissed as a functionless vestige in the adult ovary. Using PAX8 immunostaining and confocal microscopy, we characterized the fetal development of the RO in the context of the ovary. The RO consists of three distinct regions that persist in adult life, the intraovarian rete (IOR), the extraovarian rete (EOR), and the connecting rete (CR). While the cells of the IOR appear to form solid cords within the ovary, the EOR rapidly develops into a convoluted tubular epithelium ending in a distal dilated tip. Cells of the EOR are ciliated and exhibit cellular trafficking capabilities. The CR, connecting the EOR to the IOR, gradually acquires tubular epithelial characteristics by birth. Using microinjections into the distal dilated tip of the EOR, we found that luminal contents flow towards the ovary. Mass spectrometry revealed that the EOR lumen contains secreted proteins potentially important for ovarian function. We show that the cells of the EOR are closely associated with vasculature and macrophages, and are contacted by neuronal projections, consistent with a role as a sensory appendage of the ovary. The direct proximity of the RO to the ovary and its integration with the extraovarian landscape suggest that it plays an important role in ovary development and homeostasis.

  PublisherOA PDFDOI

Recent grants

• Uncovering mechanisms controlling notochord vacuole and spine morphogenesis

  NIH · $1.1M · 2013–2018

• Uncovering mechanisms controlling notochord vacuole and spine morphogenesis

  NIH · $329k · 2013–2018

• Uncovering mechanisms controlling notochord vacuole and spine morphogenesis

  NIH · $305k · 2013–2018

• Cellular and Environmental Regulation of Protein Absorption and Utilization in the Early Intestine

  NIH · $2.0M · 2019–2023

• NIH Grant DP2OD006486

  NIH · $2.3M · 2014

Frequent coauthors

• Adam R. Navis

  Taconic (United States)

  38 shared

• Jennifer Bagwell

  Duke University

  37 shared

• Daniel S. Levic

  Duke Medical Center

  29 shared

• Kenneth D. Poss

  Duke Medical Center

  27 shared

• Jennifer McKey

  University of Colorado Anschutz Medical Campus

  24 shared

• Amy L. Dickson

  18 shared

• Blanche Capel

  Duke Medical Center

  17 shared

• Dilara N. Anbarci

  Duke University

  17 shared

Education

• Ph.D., Cell Biology

  European Molecular Biology Laboratory

  2002

• BS

  Universidad Autonoma de Madrid Facultad de Ciencias

  1998