No abstract

SUMMARY Our understanding of mechanisms that regulate the differentiation of specific classes of synapses is limited. Here, we investigate the formation of synapses between hippocampal dentate gyrus (DG) neurons and their target CA3 neurons and find that DG neurons preferentially form synapses with CA3 rather than DG or CA1 neurons in culture, suggesting that specific interactions between DG and CA3 neurons drive synapse formation. Cadherin-9 is expressed selectively in DG and CA3 neurons, and downregulation of cadherin-9 in CA3 neurons leads to a selective decrease in the number and size of DG synapses onto CA3 neurons. In addition, loss of cadherin-9 from DG or CA3 neurons in vivo leads to striking defects in the formation and differentiation of the DG-CA3 mossy fiber synapse. These observations indicate that cadherin-9 bidirectionally regulates DG-CA3 synapse development and highlight the critical role of differentially expressed molecular cues in establishing specific connections in the mammalian brain.

No abstract

The bone marrow microenvironment plays an important role in promoting hematopoietic progenitor cell proliferation and differentiation and the controlled egress of these developing hematopoietic cells. The establishment of long-term bone marrow cultures, which are thought to mimic hematopoiesis in vitro, and various stromal cell lines has greatly facilitated the analysis of the functions of this microenvironment. Extracellular matrix (ECM) molecules of all three categories (collagens, proteoglycans and glycoproteins) have been identified as part of this microenvironment and have been shown to be involved in different biological functions such as cell adhesion and anti-adhesion, binding and presentation of various cytokines and regulation of cell growth. It is suggested that these matrix molecules in combination with cytokines are crucial for compartmentalization of the bone marrow. Although many cell adhesion molecules have been characterized on the surface of hematopoietic progenitor cells, the nature of cellular receptors for the ECM components is less well defined. During leukemia, many immature blood cells are released from bone marrow, but it is not yet known whether these abnormalities in hematopoiesis are also caused by an altered microenvironment or altered composition of its extracellular matrix. The elucidation of the involvement of specific ECM-isoforms and as yet not characterized ECM components and their receptors in the bone marrow will certainly help towards a better understanding of these phenomena.

When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor cells is still limited to a few applications, and it mainly applies to mesenchymal stromal cells (MSCs) isolated from bone marrow. But research progressed and different trials explore the clinical potential of human MSCs isolated from bone marrow but also from other tissues including adipose tissue. Recently, MSCs isolated from bone marrow (bmMSCs) were shown to be a blend of distinct cells and MSCs isolated from different tissues show besides some common features also some significant differences. This includes the expression of distinct antigens on subsets of MSCs, which was utilized recently to define and separate functionally different subsets from bulk MSCs. We therefore briefly discuss differences found in subsets of human bmMSCs and in MSCs isolated from some other sources and touch upon how this could be utilized for cell-based therapies.