The extracellular matrix (ECM) is much more than an inert material surrounding cells. Rather, evidence suggests that the ECM provides instructional cues regarding the external environment. One way that the ECM may act is as a reservoir for growth factors. However, specific growth factor-ECM interactions are undescribed in many instances. Recent research in the Iovine lab has identified a novel growth factor-ECM interaction that contributes to skeletal morphogenesis during fin regeneration. The fin skeleton is comprised of multiple bony fin rays, and each fin ray is comprised of bony segments separated by joints. Our research on the short fin (sof) mutant revealed that the gap junction protein Connexin43 (Cx43) coordinates skeletal growth (cell proliferation) and patterning (specification of joints). To provide insight into how Cx43 influences these cell behaviors, we identified downstream mediators of Cx43 function. Included among the Cx43-dependent genes are the secreted signaling molecule Semaphorin3d (Sema3d) and the link protein Hyaluronan and Proteoglycan Link Protein 1a (Hapln1a). Sema3d serves as a secreted growth factor that stimulates signal transduction pathways that promote cell proliferation in blastemal cells and suppress joint specification in skeletal precursor cells. Hapln1a/link protein is a component of the extracellular matrix (ECM) that is known to stabilize interactions between hyaluronan (HA) and proteoglycans (such as Aggrecan and Versican). Prior studies demonstrated that both Sema3d and Hapln1a are molecularly and functionally downstream of Cx43, as knockdown of either recapitulates the sof phenotypes (i.e. reduced cell proliferation and short segments/premature specification of joints). Current findings demonstrate that hapln1a and sema3d interact genetically, suggesting that the Hapln1a and Sema3d gene products function in a common pathway to coordinate skeletal growth and patterning. Moreover, morpholino-mediated knockdown of Hapln1a leads to reduced HA, Aggrecan, and Sema3d protein in regenerating fins. These findings suggest that Hapln1a is needed to stabilize aggregates of HA and Aggrecan, which in turn are required to stabilize Sema3d protein. Therefore, Sema3d protein levels and Sema3d-based signal transduction depend on the presence of HA-Hapln1a-Aggrecan aggregates. Overexpression of Sema3d rescues Hapln1a-knockdown phenotypes, providing further evidence that Hapln1a and Sema3d functionally interact during fin regeneration. These results are the first to demonstrate that Sema3d function requires an intact Hapln1a-ECM. Moreover, these findings reveal tangible connections between the Hapln1a-ECM, Sema3d-dependent signal transduction, and skeletal morphogenesis.