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R-spondin3 (Rspo3) is a member of the R-spondin (Rspo) protein family, which is characterized by furin-like cysteine-rich domains and a thrombospondin type 1 repeat. Rspo has been proposed as a secretory molecule capable of promoting the Wnt/b-catenin signaling pathway. Dr. Mieda isolated the zebrafish r-spondin3 (z-rspo3) as a gene downregulated by repression of Islet-3 function using subtractive hybridization. Islet-3 is a LIM/homeodomain protein expressed specifically in the embryonic midbrain. z-rspo3 is expressed in the several tissues including the midbrain/hindbrain boundary, the roof plate and the domain between the diencephalon and telencephalon.
Mouse Rspo3 is also expressed in the roof plate and the domain between the diencephalon and telencephalon during development (Fig.1. A-E). This pattern of expression is highly conserved among Rspo family members (Fig.2), implying an important role for Rspo in embryonic brain development. Rspo3 is also expressed in the several tissues, including the limbs and the outflow tract and atrioventricular boundary of the developing heart (Fig.1. F-J). Rspo2 is specifically expressed in the apical ectodermal ridge (AER) (Fig.2. B). We analyze the Rspo-deficient mice to find the Rspo gene function.