Collagen remodeling supports Hydra vulgaris head regeneration and stem cell invasion.

The freshwater cnidarian Hydra vulgaris is a classic model for studying whole-body regeneration, but the underlying cell biology remains comparatively underexplored. Hydra has a simple body plan consisting of two epithelial monolayers separated by an extracellular matrix (ECM) containing conserved components such as collagen and laminin, making it well suited for investigating ECM function during regeneration. Following head amputation, collagen and laminin retract from the wound site, generating a region of low ECM accumulation that persists for several days. Multiple matrix metalloproteinase (MMP) genes are expressed in the endoderm during this process, and MMP inhibition reduces the size of the collagen-depleted region and disrupts head morphogenesis. In contrast, inhibition of collagen cross-linking also blocks regeneration, indicating that successful regeneration requires a balance between ECM degradation and deposition. Finally, invasion of interstitial stem cell progenitors from the ectoderm into the endoderm during regeneration is facilitated by MMP-driven reduction of Collagen I. Together, these findings identify ECM remodeling as a crucial and conserved feature of regeneration, and establish Hydra as a valuable model for studying its underlying mechanisms.