How matrix proteins precisely control the growth of nacre lamellae is an open question in biomineralization research. Using the antibodies against matrix proteins for immunolabeling and in vivo experiments. we investigate the structural and functional roles of EDTA-soluble matrix (SM) and EDTA-insoluable matrix (ISM) proteins in nacre biomineralization of the pearl oyster Pinctada fucata. Immunolabeling reveals that a SM proteins, nacrein, distributes within aragonitic tablets and intertabular matrix. An ISM protein. Which we named P43, has been specifically recognized by polyclonal antibodies raised against the recombinant protein of P.fucata bone morphogenetic protein 2 in immunoblot analysis. Immunolabeling indicates that P43 is localized to interlamellar sheet and also embedded within aragonitic tablets. Although nacrein and P43 both distribute within aragnoitic tablets, they function differently in aragonitic tablet growth. When nacrein in suppressed by the antibodies agaisnt it in vivo, crystal over-growth occurs, indicating that this SM protein is a negative regulator in aragonitic tablet growth. When P43 is suppressed in vivo, the organo-mineral assemblage is distrupted, suggesting that P43 is a frame-work matrix. Taken together, SM and ISM proteins are indispensable factors for the growth of nacre lamellae, controlling crystal growth and constructing and the framework of aragonitic tablets. (c) 2008 Elsevier Inc. All rights reserved.