本研究は，皮膚の真皮コラーゲンは線維芽細胞が作るという従来の常識を覆し，表皮細胞がＩ型コラーゲンを供給するという発見を出発点とするものである．表皮と真皮の境界には，分子透過を制限する基底膜が存在する．では，巨大分子であるコラーゲンはどのようにこの膜を越え，真皮側で秩序ある線維網を形成するのか．本研究では，細胞が大きく顕微観察に適したアホロートル（ウーパールーパー）を用い，GFP標識コラーゲン，高解像SEM，超解像顕微鏡，免疫電顕などを組み合わせて，この問いに挑む．特に，基底膜がコラーゲン分子の向きをそろえて通過を助ける「分子篩」として働く可能性，また成熟酵素を真皮側に留める「分子選択層」として働く可能性を検証する．さらに，ヒト細胞で得た共培養実験の知見と照合し，表皮側では線維化せず，基底膜直下でのみ成熟と会合が進む仕組みを多面的に解析する．独自のウイルス発現系も活用し，分子動態を生体組織内で追跡する．これにより，基底膜を単なるバリアではなく，細胞外マトリックス形成を制御する能動的な場として捉え直し，皮膚形成，再生，瘢痕抑制，抗老化研究に新たな基盤を提示し，学術変革領域の推進にも貢献するものである．

This study is based on a discovery that overturns the conventional view that dermal fibroblasts produce dermal collagen in the skin, showing instead that epidermal cells supply type I collagen. At the boundary between the epidermis and dermis lies the basement membrane, a structure that restricts molecular permeability. How, then, does collagen, a giant molecule, cross this membrane and form an ordered fibrous network on the dermal side? To address this question, this study uses the axolotl, whose large cells are well suited for microscopic observation, and combines GFP-labeled collagen, high-resolution scanning electron microscopy, super-resolution microscopy, and immunoelectron microscopy. In particular, it will test the possibility that the basement membrane functions as a “molecular sieve” that aligns collagen molecules and facilitates their passage, as well as the possibility that it acts as a “molecular selection layer” that retains maturation enzymes on the dermal side. In addition, by comparing these observations with findings from human cell co-culture experiments, the study will analyze, from multiple perspectives, the mechanism by which collagen does not fibrillate on the epidermal side but instead matures and assembles only directly beneath the basement membrane. An original viral expression system will also be used to trace molecular dynamics within living tissue. Through these approaches, this study will redefine the basement membrane not merely as a barrier, but as an active site that regulates extracellular matrix formation, thereby providing a new foundation for research on skin formation, regeneration, scar suppression, and anti-aging, while also contributing to the advancement of the Transformative Research Area.