Syncytia are multinucleated cells that form distinct functional compartments. It is not well understood how these compartments are generated and how proteins are able to spatially localize within a syncytium. Here, Charles Ettensohn and colleagues use the sea urchin embryonic skeleton to study how specialized compartments are generated in a syncytium to give rise to local skeletal patterns. First, the authors express fluorescently tagged forms of several transcription factors and biomineralization proteins in sub-domains of the syncytium. They observe that the fluorescently tagged proteins have restricted distribution within the syncytium. Next, the authors ask whether proteins translocate over long distances to reach the specific sub-domains or remain near the site of translation. They carry out in situ hybridization combined with immunofluorescence staining and find that the restricted distribution is due to the tendency of proteins to remain near where they are synthesized. Furthermore, the authors find that the DNA-binding domains in transcription factors are necessary to limit mobility, while the N-terminal signal sequences and transmembrane domains of biomineralization proteins limit their diffusion. Overall, the findings suggest that limited mobility of molecules generates subdomains of protein expression within the syncytium, ultimately leading to local patterns of skeletal growth.