Molecular and cellular insights into the coxsackie-adenovirus receptor: role in cellular interactions in the stem cell niche

In recent years, progress has been made in characterizing the molecular and cellular elements that are responsible for the regeneration in the damaged brain and highlighting the key role of the stromal-vascular 'environment' to orchestrate secondary neurogenesis and repair. Indeed, the ability of the stem cells to self-renew and differentiate is tightly regulated by stromal ependymal cells and endothelial cells expressing molecular cues that constitute the extracellular stem cell 'niche'. Several soluble growth factors such as EGF, TGFβ, FGF2, SDF-1α and Noggin are important signals for the stem cell niche but little is known about the role of membrane-bound molecules in intercellular communications between the niche and the stem cells. In this mini-review, we highlight the emerging role of a family of adhesion molecules in the control of secondary neurogenesis. The coxsackie-adenovirus receptor (CAR) is a 46 kDa transmembrane protein and a member of the immunoglobulin super family. It is close structurally and evolutionary to other adhesion molecules involved in cell-cell interactions during embryogenesis, broadly expressed in the developing central nervous system but restricted to ependymal cells in the adult brain. This unique location and its newly established signalling properties further support the role of CAR in intercellular communications. Elucidating the other signalling molecules and manipulating the stromal-vascular niche for example by adenovirus gene therapy remain important goals for future clinical applications.