Determination of Expression Profiles and Regulatory Elements for Slit2 with Gene Expression and Genomic Databases

In previous studies we found that the expression of Slit2 is directly proportional to total hematopoietic stem cell (HSC) numbers in mice. Understanding the regulatory elements governing Slit2 expression and Slit2 function in cells will facilitate manipulation of the gene and improve our understanding of HSC biology. We used in silico analysis of expressed sequence tags and microarray databases to determine expression patterns for Slit2 and the Robo gene family. In all profiled species, we found a consistent, negative correlation between Slit2 expression and maturation from embryo to adulthood, indicating that expression of Slit2 is evolutionarily conserved and linked to development and proliferation of cells. In most cases where Slit2 is expressed in a tissue, Robo4 is expressed at least minimally, suggesting Robo4 could be the receptor of Slit2 in HSCs. In ongoing studies of genomic databases, we are aiming to detect conservation of certain transcription factor binding sites (TFBS) between species. For transcription factors of interest, we have identified some conservation of TBFS between mice and humans, but further testing and experimentation will be necessary to determine if those TFBS affect the differential expression of Slit2.