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Proteolytic Control of Neuronal Differentiation

$44,212F32FY2002HDNIH

University Of California Los Angeles, Los Angeles CA

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Abstract

We have discovered a secreted, soluble protein that is able to inhibit primary neurogenesis in Xenopus embryos. This 394 amino acid protein contains three serine proteinase inhibitor domains of the Kunitz class. This novel protein has been named Trinein and was isolated during a differential screen for maternally-encoded mRNAs present in the Xenopus laevis egg. Strikingly, microinjection of Trinein mRNA into Xenopus embryos seems to have little effect on mesodermal (marked by Xbra, sonic hedgehog, chordin) and neural plate (marked by Sox-2) cell differentiation; however, differentiation of definitive mature neurons (positive for neurotubulin and neurogenin) is blocked in the neural plate (unpublished data). This proposal builds upon these functional data of Trinein to understand its function in mammalian neurogenesis.

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