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During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demonstrated that a subset of Osr1- expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneity of Osr1+ cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation. [Display omitted] • Osr1 labels mLTo cells and progenitors for adult mesenchymal LN stromal cells • Identifies a common progenitor of mesenchymal LTo cells and LN-associated adipose tissue • Osr1 is required for mesenchymal LTo cell commitment via retinoic acid signaling • Osr1+ cells control LEC assembly, and mLTo-LEC combined action leads to LN initiation The initial step of lymph node (LN) formation relies on lymphoid tissue organizer (LTo) cells, which are poorly characterized. Vallecillo-García et al. reveal that Osr1 labels mesenchymal LTo cells and their progenitors, is essential for their commitment via retinoic acid signaling, and is required for LN-associated lymphatic vasculature assembly. [ABSTRACT FROM AUTHOR]