Tuberculosis (TB) kills 1.5 million people annually, with 8-9 million new active cases each year. The causative agent, Mycobacterium tuberculosis (Mtb), manipulates host macrophages to survive within them. These infected macrophages, along with uninfected macrophages and other immune cells, aggregate into characteristic structures called granulomas where almost all bacteria reside in human Mtb infections. We have paired Mycobacterium marinum (Mm), the closest relative of the Mtb complex and a natural pathogen of ectotherms, with the zebrafish to establish a validated surrogate for human TB. The tuberculous granulomas that form in zebrafish recapitulate important features of human granulomas (organization, hypoxia, caseation necrosis) that are absent from standard mouse models. Here, we use the zebrafish to investigate how the central structure of mycobacterial infection is assembled and remodeled. We have used this model to make new findings about the tuberculous granuloma and have validated these findings in human specimens. Here, based on these findings and preliminary data, we hypothesize that macrophages, the central immune reservoir for pathogenic mycobacteria, deploy canonical developmental pathways, not traditionally considered in the context of immunity, in the construction of the granuloma. Using the zebrafish- Mycobacterium marinum model we will determine the role of developmental signaling in mycobacterial pathogenesis and granuloma formation.