Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics

First Advisor

Nicoli, Stefania

Abstract

Epidermal stem cells interact with the extracellular matrix (ECM) to regulate their differentiation and maintain skin architecture. Yet, it remains unclear whether these interactions extend beyond cell fate determination to influence broader skin functions. Here, we demonstrate that the protective, mechanically shielding properties of the periderm—the superficial epidermal cells (SECs) of the embryonic bilayered skin— are orchestrated by interactions between the underlying undifferentiated basal epidermal stem cells (BECs) and the ECM. Using the developing zebrafish fin fold, we identify that BECs form distinct collagen- versus laminin- enriched basement membranes, enabling the SECs above the BEC-laminin areas to close wounds faster following injury. Mechanistically, collagen-associated BECs form desmosomes and adherens junctions with SECs. In contrast, laminin-associated BECs display reduced desmosomes but sustain adherens junctions and actomyosin tension with SECs, creating distinct mechanical zones in the fin fold. Disrupting integrin-mediated adhesions between BECs and ECM alters the junctional organization of the outer layer periderm without affecting BECs differentiation. Notably, in a bilayered human keratinocyte model, we found that laminin, compared to collagen proteins, are sufficient to repress desmosome formation while sustaining adherens junctions specifically at the interlayer junctions. Correspondingly, in vivo, laminin deficiency increases desmosome formation, reduces actomyosin tension, and compromises the enhanced wound-healing of SECs associated with laminin-enriched BECs. Overall, our findings identify that stem cells, through their matrix, establish specialized junctions in the overlying stratified epithelium, thereby regulating skin healing properties independent of canonical differentiation processes.

Download

Share

COinS