On February 19, 2026, Ali May, an assistant professor at the Icahn School of Medicine at Mount Sinai, delivered a compelling presentation on her groundbreaking research regarding the role of tissue resident macrophages in the development of embryonic salivary glands. As part of the Department of Biology Seminar Series, May’s work challenges traditional perspectives on macrophages, highlighting their potential as active contributors to organ development rather than merely as defenders against infection.
May initiated her talk by addressing the common misconception that macrophages function solely as “garbage collectors,” tasked with engulfing dead cells and debris. Instead, she urged her audience to reconceptualize these immune cells as dynamic players in developmental processes, capable of communicating with epithelial cells, nerves, and surrounding supportive tissues. Her insights stem from her postdoctoral research on the intersection of immune and nervous systems during development, where she discovered the intricate roles these cells play in shaping tissue architecture.
By employing innovative techniques such as live imaging, genetic depletion, and organ culture, May’s laboratory investigates how distinct populations of macrophages influence branching morphogenesis—the characteristic tree-like growth seen in many glandular organs. The primary method utilized involves an inducible genetic system that selectively removes macrophages during critical phases of salivary gland development.
The findings from her research indicate that the absence of macrophages leads to less branching in developing salivary glands. May explained, “When you have less branching, you’re going to have much larger buds and fewer of them,” in contrast to the typical formation of smaller, more numerous buds in a highly branched gland. This abnormality manifests as ‘Terminal Buds,’ which signify impaired branching morphogenesis and structural anomalies within the epithelial compartment. Subsequent gene expression analyses corroborated that tissues devoid of macrophages exhibited reduced expression of genes linked to the differentiation of secretory acinar cells, ductal cells, and other essential epithelial markers.
“Not only are we reducing branching,” May noted, “but we’re hindering differentiation of these essential cells.” Beyond the impacts on epithelial structures, glands lacking macrophages also showed developmental consequences on non-epithelial cell types, suggesting a complex interplay between various cell populations within the developing salivary gland.
As part of her research, May identified signaling pathways potentially involved in this process. Utilizing single-cell RNA sequencing data, her team focused on the expression of tumor necrosis factor (TNF), a cytokine often associated with inflammation. Despite its well-known role in adult tissues, May highlighted that TNF could also act as a developmental regulator. Direct tissue staining revealed TNF expression in macrophages located near the epithelial compartment, with a significant upregulation of the epithelial TNF receptor during development.
To further investigate TNF’s effects on epithelial maturation, May’s team isolated the epithelial components of embryonic salivary glands and cultured them in vitro. The results were striking: epithelial explants treated with TNF exhibited pronounced branching and growth. May described these observations, stating, “We see a significant increase in both the branching and the growth of these glands.”
In her concluding remarks, May elaborated on the distinct origins of macrophages within salivary glands, noting two populations: a long-lived yolk-sac derived type and a monocyte-derived population that appears later in development. She presented live imaging that depicted macrophages crossing the basement membrane and enveloping epithelial cells in a behavior she referred to as “cuddling.” This interaction raises intriguing questions about whether macrophages are monitoring dividing cells or actively promoting proliferation.
May’s research presents a paradigm shift in understanding macrophages, demonstrating their crucial and multifaceted roles in organ development. Her ongoing investigations aim to unravel the complexities of how macrophages coordinate epithelial and neuronal patterns within developing tissues, reinforcing the idea that these immune cells are far more than passive bystanders in biological processes.
