Repair and regeneration of the pronephric kidney in Xenopus laevis tadpoles.
Abstract: The kidney is a unique organ in that it develops through three
distinct forms of increasing complexity, with the most embryonic form (pronephros) serving
as the functional organ in the tadpoles of the amphibian model system,
Xenopus laevis, and the most complex form (metanephros) being
found in adult humans. Since the developmental programs that govern organogenesis in all
three kid... read moreneys are conserved, and all kidneys share the same structural units and basic
functions, we can utilize these simpler pronephric kidneys to investigate the repair
mechanisms in induced renal damage. To accomplish this, we developed a novel pronephrectomy
technique to excise specific parts of the kidney in X. laevis
tadpoles, and examined the repair responses that followed. The results of these studies
demonstrate for the first time that an amphibian pronephros is able to regenerate lost
structures. We also begin to elucidate the mechanisms through which this regenerative
phenomenon occurs, and have revealed dualistic roles for the extracellular matrix
remodeler, Matrix metalloproteinase-9. This protease is expressed during two distinct
windows of pronephric regeneration: immediately after injury, and again five days later.
While the early expression of XMMP-9 promotes pronephric regeneration, proteolytic activity
of this enzyme during the second phase appears to inhibit this regenerative process. In
this dissertation, we propose likely mechanisms for these disparate roles of
Thesis (Ph.D.)--Tufts University, 2013.
Submitted to the Dept. of Biology.
Advisor: Kelly McLaughlin.
Committee: Harry Bernheim, Juliet Fuhrman, Michael Levin, Mitch McVey, and Iain Drummond.
Keywords: Biology, and Developmental biology.read less