Stay or stray: Lpar1 regulates neutrophil retention and epidermal homeostasis in early zebrafish development.

Neutrophils play essential roles in host defense, but the mechanisms governing their developmental distribution remain poorly understood. Here, we identify a previously unrecognized function of lysophosphatidic acid receptor 1 (Lpar1) in maintaining neutrophil retention during early zebrafish development. Contrary to its previously described pro-inflammatory role, Lpar1 acts in an anti-inflammatory manner by preventing premature neutrophil dispersal. Mechanistically, Lpar1 regulates the expression of cxcl12a in the caudal hematopoietic tissue (CHT), establishing a novel Lpar1-Cxcl12a signaling axis that governs neutrophil localization. Lpar1 also influences neutrophil mobility through its effects on vascular integrity in the CHT, which is severely disrupted in Lpar1 morphants but may be mildly affected in Lpar1 mutants. Dispersed neutrophils are predominantly recruited to the superficial epidermal layer, where numerous apoptotic cells are present. Collectively, these findings refine current models of immune regulation during development and reveal an alternative mechanism that may contribute to the development of inflammatory skin disorders.