Brain-specific Angiogensis Inhibitor-1(BAI1) Molecular Biological Function Research In The Differentiation Of Neuronal Precursor Cells

Brain-specific angiogenesis inhibitor-1(BAI1) encodes a seven- transmembrane protein that belongs to the adhesion-GPCR family. It is highly expressed in normal brain and has three apparently distinct functions. First, anti-angiogenesis function for fragment cleaved from extracellular BAI1. Second, BAI1 cooperates with ELMO1/DOCK180/Rac to promote engulfment of apoptotic cells. Third, BAI1 enrich in the postsynaptic density regulate its development by active both the Rho and ERK pathway. Article identified a phagocytic role for the DCX+ neuronal progenitor cells during adult neurogenesis. They use a phosphatidylserine dependent recognition for uptake. Intracellular engulfment protein engulfment and cell motility 1(ELMO1) was required for phagocytosis by DCX+ cells. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX+ cells. Disruption of engulfment in vivo genetically(in Elmo1-null mice) or pharmacologically(in wild-type mice) led to reduced uptake by DCXC cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. However, the receptor(s) are still unknown.As the function and distribution of BAI1, we hypothesize that BAI1 may be an engulfment function of the DCX+ neuronal progenitor cells. We have planed several experiments to identify the results. We detected the expression of BAI1 on DCX+ neuronal progenitor cells. BAI1 antibody can reduce the activity of engulfment of DCX+ neuronal progenitor cells. At the same time, we discover that BAI1 antibody can affect the differentiation and development of neural stem cells to DCX+ neuronal precursor cells. Higher concentration and earlier add BAI1 antibody to the neural stem cells, the greater influence to its differentiation. Even, add BAI1 antibody in the first 6 hours, will not be able to differentiate into DCX+ neuronal precursor cells. PPARγ control inflammatory reaction as well as increase the engulfment receptor expression to expand the effect in the engulfment process. The PPARγ agonists and inhibitors can significantly affect the the differentiation and phagocytosis of neural stem cells as well as the expression of BAI1.Otherwise BAI1 is a classical tumor suppressor factor and it is associated with a variety of cancer diseases. Because of the different aspects of the physiological function and its distribution in the brain, it may be a new breakthrough to solve the neurological diseases.