Here, we discovered that constitutive β-catenin activation specifically in BM-SEC caused aberrant sinusoidal endothelial differentiation with altered EC marker gene expression and increased periendothelial ECM deposition as well as angiocrine dysregulation with de novo expression of FGF23 and DKK2. Aberrant sinusoidal differentiation and angiocrine dysregulation entailed lethal anemia due to a block in terminal erythroid differentiation resulting in defective reticulocyte maturation. This evidence concerns the gene DKK2 and anemia.