The human COL17A1 gene encodes type XVII collagen (also known as the 180-kDa bullous pemphigoid antigen), an integral component of hemidesmosomes, attachment complexes providing integrity to the dermal-epidermal junction. Zebrafish, a useful model system to study skin development, displays fully developed hemidesmosomes at approximately 5 days post-fertilization (dpf). We have identified two COL17A1 orthologues in the zebrafish genome, col17a1a and col17a1b, which are expressed in the skin and the neural system, respectively. The proteins coded by these genes have structural module organizations homologous to the human type XVII collagen. "Knock-down" of the expression of col17a1a with a specific morpholino targeting the 5' UTR of the gene resulted in a blistering phenotype and in perturbations in the basement membrane zone. "Knock-down" of col17a1b expression resulted in ablation or in marked reduction of neuromasts in the lateral line. Thus, zebrafish has two COL17A1 orthologues which may have evolved tissue-specific functions during vertebrate development. Collectively, zebrafish provides a model system to study the molecular aspects of skin development and offers insights into the corresponding human diseases.
Bibliographical noteFunding Information:
The authors wish to thank GianPaolo Guercio, Adele Donahue, and Carol Kelly for assistance. Dr. Ulrich Rodeck provided expert advise. This study was supported by the Dermatology Foundation and the Pilot Research Award programs of Thomas Jefferson University to QL. CHK was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare , Republic of Korea ( 1020090 ).
- Morpholino "knock-down"
- Type XVII collagen
- Zebrafish development