RRC ID 2526
Author Suzuki M, Satoh A, Ide H, Tamura K.
Title Transgenic Xenopus with prx1 limb enhancer reveals crucial contribution of MEK/ERK and PI3K/AKT pathways in blastema formation during limb regeneration.
Journal Dev Biol
Abstract Understanding the mechanisms that control amphibian limb regeneration should allow us to decipher the critical differences between amphibians and humans, which have the limited ability of organ regeneration. However, many issues at the cellular and molecular levels still remain unresolved. We have generated a transgenic Xenopus laevis line that expresses green fluorescent protein (GFP) under the control of mouse prx1 limb enhancer, which directs reporter gene expression in limb mesenchyme in mice, and found that GFP accumulated in blastemal mesenchymal cells of the transgenic froglets after limb amputation. Thus, this transgenic line should provide a new approach to gain insights into the cellular dynamics and signaling pathways involved in limb blastema formation. We have also developed a culture system for forelimb explants of froglets and found that treatment with inhibitors of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) kinase 1/2 (MEK1/2) and phosphatidylinositol 3-kinase (PI3K) repressed GFP expression. These effects were partially reversible, and down-regulation of GFP was associated with inhibition of cell-cycle progression and induction of ectopic apoptosis. In addition, we found that ERK1/2 and AKT, downstream mediators of MEK1/2 and PI3K pathways, were activated in amputated forelimb stumps. These results demonstrate that MEK/ERK and PI3K/AKT pathways regulate limb blastema formation in the X. laevis froglet.
Volume 304(2)
Pages 675-86
Published 2007-4-15
DOI 10.1016/j.ydbio.2007.01.019
PII S0012-1606(07)00035-8
PMID 17303106
MeSH Animals Animals, Genetically Modified Enhancer Elements, Genetic Extremities / physiology* Homeodomain Proteins / genetics* Homeodomain Proteins / metabolism MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Mice Phosphatidylinositol 3-Kinases / physiology* Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / physiology* Regeneration* Signal Transduction Tissue Culture Techniques Xenopus laevis / genetics Xenopus laevis / physiology*
IF 2.896
Times Cited 42
Clawed frogs / Newts