EN
Dendritic arborization patterns define neuronal subtypes, and have important functional implications, determining how signals coming from individual synapses are integrated. Developing dendrites of neurons are responsive to extrinsic signals. Although several secreted proteins, cell surface receptors and adhesion molecules have been recently shown to be involved in dendrite morphogenesis, the role of extracellular matrix (ECM) components and molecular mechanisms of signal transduction from ECM to the neuronal cells involved in these processes are still poorly understood. The main component of the ECM in the brain is hyaluronan (HA). The major receptor for hyaluronan is CD44 adhesion molecule which mediates the response of cells to their extracellular microenvironment. The aim of this study was to investigate the role of CD44 in regulation of dendritic tree arborization. First, we examined the expression pattern of CD44 at the protein and RNA level in the rat brain by immunohistochemical, in situ hybridization and in situ PCR assays. All our experimental approaches clearly point to the neuronal localization of CD44, in addition to widely accepted presence in glia. Next, we investigated the role of CD44 in the hippocampal neurons cultured in vitro using the shRNA technology and anti-CD44 function-blocking antibody. The morphometric analysis show that cells with diminished expression of CD44 have more complex dendritic tree then control cells. Moreover, we have shown that treatment of neuronal cells with CD44 blocking antibody caused activation of small Rho GTPases (Cdc42, Rac1 and RhoA), which were previously shown to regulate dendritic tree arborization. These observations indicate that the members of small Rho GTPase family can be downstream effectors of CD44 in neuronal cells. The results of our experiments point to the importance of CD44 protein for the development of dendritic tree.