English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis

MPS-Authors
/persons/resource/persons191008

Carney,  Thomas J.
Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191366

von der Hardt,  Sophia
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191328

Sonntag,  Carmen
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191086

Hammerschmidt,  Matthias
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Carney, T. J., von der Hardt, S., Sonntag, C., Amsterdam, A., Topczewski, J., Hopkins, N., et al. (2007). Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis. Development, 134, 3461-3471.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-91A3-F
Abstract
Epithelial integrity requires the adhesion of cells to each other as well as to an underlying basement membrane. The modulation of adherence properties is crucial to morphogenesis and wound healing, and deregulated adhesion has been implicated in skin diseases and cancer metastasis. Here, we describe zebrafish that are mutant in the serine protease inhibitor Hai1a (Spint1la), which display disrupted epidermal integrity. These defects are further enhanced upon combined loss of hai1a and its paralog hai1b. By applying in vivo imaging, we demonstrate that Hai1-deficient keratinocytes acquire mesenchymal-like characteristics, lose contact with each other, and become mobile and more susceptible to apoptosis. In addition, inflammation of the mutant skin is evident, although not causative of the epidermal defects. Only later, the epidermis exhibits enhanced cell proliferation. The defects of hai1 mutants can be phenocopied by overexpression and can be fully rescued by simultaneous inactivation of the serine protease Matriptase1a (St14a), indicating that Hai1 promotes epithelial integrity by inhibiting Matriptase1a. By contrast, Hepatocyte growth factor (Hgf), a well-known promoter of epithelial-mesenchymal transitions and a prime target of Matriptase1 activity, plays no major role. Our work provides direct genetic evidence for antagonistic in vivo roles of Hai1 and Matriptase1a to regulate skin homeostasis and remodeling.