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Proc Natl Acad Sci U S A May 15, 2007; 104 (20): 8502-7.
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Caspase-9 regulates apoptosis/proliferation balance during metamorphic brain remodeling in Xenopus.

Coen L , Le Blay K , Rowe I , Demeneix BA .

During anuran metamorphosis, the tadpole brain is transformed producing the sensorial and motor systems required for the frog''s predatory lifestyle. Nervous system remodeling simultaneously implicates apoptosis, cell division, and differentiation. The molecular mechanisms underlying this remodeling have yet to be characterized. Starting from the observation that active caspase-9 and the Bcl-X(L) homologue, XR11 are highly expressed in tadpole brain during metamorphosis, we determined their implication in regulating the balance of apoptosis and proliferation in the developing tadpole brain. In situ hybridization showed caspase-9 mRNA to be expressed mainly in the ventricular area, a site of neuroblast proliferation. To test the functional role of caspase-9 in equilibrating neuroblast production and elimination, we overexpressed a dominant-negative caspase-9 protein, DN9, in the tadpole brain using somatic gene transfer and germinal transgenesis. In both cases, abrogating caspase-9 activity significantly decreased brain apoptosis and increased numbers of actively proliferating cells in the ventricular zone. Moreover, overexpression of XR11 with or without DN9 was also effective in decreasing apoptosis and increasing cell division in the tadpole brain. We conclude that XR11 and caspase-9, two key members of the mitochondrial death pathway, are implicated in controlling the proliferative status of neuroblasts in the metamorphosing Xenopus brain. Modification of their expression during the critical period of metamorphosis alters the outcome of metamorphic neurogenesis, resulting in a modified brain phenotype in juvenile Xenopus.

PubMed ID: 17488818
PMC ID: PMC1895979
Article link: Proc Natl Acad Sci U S A

Species referenced: Xenopus laevis
Genes referenced: bcl2l1 casp3.2 casp9 gnl3 hopx tub

Article Images: [+] show captions
References [+] :
Alenzi, Links between apoptosis, proliferation and the cell cycle. 2004, Pubmed