title: Caspase-14 but not caspase-3 is processed during the development of fetal mouse epidermis.
abstract: The activation of caspases is a central step in apoptosis and may also be critical for terminal differentiation of epidermal keratinocytes (KC). In particular, caspase-3 has been implicated in the differentiation of embryonic KC as well as in programmed cell death of KC, and caspase-14 has been suggested to function in the formation or homeostasis of the stratum corneum (SC). To test the putative roles of these proteases, we determined their expression level and activation status during development of fetal mouse epidermis. The level of procaspase-3 did not change significantly during epidermal development, and enzyme activation was undetectable at any timepoint investigated. Despite the lack of active caspase-3, the newly formed stratum granulosum and the regressing periderm contained cells positive in the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay, indicating that nuclear DNA was degraded without activation of caspase-3, thereby arguing against a proteolytic function of caspase-3 in embryonic KC differentiation. By contrast, caspase-14 increased in abundance from embryonic day 14.5 (E14.5) onwards and consistently localized to the suprabasal layers of fetal epidermis. The caspase-14 pro-enzyme was processed into its catalytic subunits, a step required for enzyme activity, on day E17.5, coinciding with SC formation. Thus, processing of procaspase-14 is not confined to air-exposed mature skin but also occurs during epidermal development in utero. In summary, this study demonstrates that caspase-14, but not caspase-3 activation coincides temporally and spatially with embryonic KC differentiation, suggesting a role for caspase-14 in terminally differentiated KC.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Fischer
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Rossiter
authors.forename: Minoo
authors.initials: M
authors.lastname: Ghannadan
authors.forename: Karin
authors.initials: K
authors.lastname: Jaeger
authors.forename: Caterina
authors.initials: C
authors.lastname: Barresi
authors.forename: Wim
authors.initials: W
authors.lastname: Declercq
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
mesh_terms: D000818:Animals; D053456:Caspase 14; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation; D004789:Enzyme Activation; D004817:Epidermis / Q000196:embryology* / Q000201:enzymology*; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D051379:Mice
chemical_list: C506449:Casp14 protein, mouse; C505409:Casp3 protein, mouse; D053456:Caspase 14; D053148:Caspase 3; D020169:Caspases