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Louveau, A.

Publications and source records attributed to Louveau, A..

3 recordsLinked to original sources

A new Mmrn1-CreERT2 Mouse Model for High-Fidelity Labeling of Adult Lymphatic Endothelium

Cell type-specific Cre driver lines are essential for studying organ-specific biology in vivo, but recombination in unintended targets can limit their interpretive power. The dural meninges harbor a distinct network of lymphatic vessels implicated in neurological processes ranging from neurodevelopment to neurodegeneration. Current lymphatic reporters, driven by Prox1, Lyve1 or Vegfr3, efficiently recombine in lymphatic endothelial cells, including in the dura, but are also expressed in other CNS cell populations, resulting in non-lymphatic recombination that complicates interpretation. Here, we identify Mmrn1 as a gene specifically enriched in lymphatic endothelial cells throughout the body, with no detectable expression in other CNS cells. We generated an Mmrn1CreERT2 mouse line and show that, in adult mice, it drives recombination restricted to lymphatic endothelial cells, with no detectable recombination in non-lymphatic CNS populations. A similar but less complete recombination is observed in developing mice. This tool offers the lymphatic field a new means to specifically manipulate lymphatic vasculature and study its cell-specific functions.

neuroscience↗

Lymphatic CD49a is a driver of meningeal immune aging and cognitive decline.

Aging is associated with progressive accumulation and dysregulation of dural immune cells, coinciding with impaired CSF drainage and lymphatic function. Prior work has shown that improving lymphatic function in aged mice is sufficient to ameliorate age-associated cognitive decline, and that local immune cells can directly regulate lymphatic draining function. Yet, the endothelial-intrinsic mechanisms driving lymphatic dysfunction remain unclear. Here we found that the integrin CD49a is upregulated in aged lymphatic endothelial cells and regulates CCL21 release. Accordingly, genetic deletion of CD49a in lymphatic endothelial cells broadly reverses age-associated immune dysfunction across dural myeloid, lymphoid and dendritic cell compartments, limits glial aging, and mitigates cognitive and social behavioral deficits, thereby revealing a targetable endothelial-intrinsic mechanism of lymphatic aging.

neuroscience↗

A Single-Cell Atlas of the Mouse Dural Meninges Reveals Pervasive Sex Differences Across Cellular Compartments

The dural compartment of the meninges forms a dynamic interface between the brain and the periphery, hosting diverse immune, vascular, mural and fibroblast populations. Single-cell studies have begun charting meningeal cellular diversity, yet a comprehensive view encompassing all major cellular compartments, intercellular communication, and the influence of sex remains lacking. Here, we present a single-cell transcriptomic atlas of the adult mouse dural meninges, profiling all major cell types in male and female mice at steady state. We uncover broad sex differences in cell-type-specific proportion, transcriptional programs, intercellular communication, and disease relevant signatures. Histological and cytometry analyses validate the biological relevance of these findings, establishing this atlas as a foundation for studying meningeal contributions to neurological disease in a sex-aware manner.

neuroscience↗