The vomeronasal organ (VNO) is an olfactory structure responsible for detecting chemical cues, such as pheromones, important for communication within and between species. Vomeronasal sensory neurons are short-lived and continuously replaced from a stem cell (SC) niche. Previously, Eva Neuhaus and colleagues identified the C-X-C chemokine receptor 4 (CXCR4) as a regulator of neurogenesis in the olfactory epithelium. Here (Dietz et al., 2025), the same research group demonstrates a role for CXCR4 signalling in VNO development. The authors combine RNA sequencing, bioinformatics, immunofluorescence and lineage tracing to show that CXCR4 is expressed in proliferative SCs, neuronal precursors and basal VSNs. Additionally, conditional knockout (cKO) of Cxcr4 in globose basal cells, the primary VNO stem cell population, results in increased expression of proliferative SC markers (SOX2 and MCM2) and a reduction in DCX, a marker of neuronal differentiation. Surprisingly, Cxcr4 cKO also disrupts the differentiation of non-neuronal cell types in the VNO, highlighting the dual role of CXCR4 in regulating both neuronal and non-neuronal cell fate. Finally, they employ computational gene perturbation analysis to simulate the effects of disrupted neuronal differentiation in the VNO and identify several transcription factors potentially involved in neurogenesis. This study highlights the crucial role of CXCR4 in maintaining VNO sensory neuron homeostasis and provides valuable insights into olfactory neurogenesis and regeneration.
