| Popis: |
Extracellular matrix (ECM) remodeling by metalloproteinases is crucial during development. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin type I motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling. The human family includes 19 members. In this study Xenopus was used as an in vivo model for studying the function of ADAMTSs during development. 19 members of the ADAMTS family were identified in Xenopus. A phylogenetic study and synteny analysis revealed strong conservation of the ADAMTS family, provided a view of the evolutionary history and contributed to a better annotation of the Xenopus genomes. The expression of the ADAMTS family was studied from early stages to tadpole stages of Xenopus with a focus on ADAMTS9 showing expression in neural crest (NC) derivative tissues and in the pronephros ADAMTS9 function was investigated in these structures. ADAMTS9 knock-down does not affect NC migration but causes a phenotype in the pronephros defined by a delay of development from early tailbud stage of pronephric nephrostomes, tubules and duct. Versican, a matrix component substract of ADAMTS9, is expressed in the pronephros at tailbud stage but not at tadpole stage suggesting a transient role during development. The lack of its degradation by ADAMTS9 could be the cause of the delay of pronephros development. The expression of the ADAMTS family as well as other metalloproteinases, ECM components and tissue inhibitor of metalloproteinases was studied in the skin, the brain and the heart undergoing remodeling during Xenopus laevis metamorphosis, as well as in the heart after ventricular resection to look at regeneration during Xenopus laevis metamorphosis. The results showed specific gene regulation depending on the stage of development and in response to heart injury revealing an important role for the ECM and its remodeling during these processes. |
