β1-integrin alters ependymal stem cell BMP receptor localization and attenuates astrogliosis after spinal cord injury

Astrogliosis after spinal cord injury (SCI) is a major impediment to functional recovery. More than half of new astrocytes generated after SCI are derived from ependymal zone stem cells (EZCs). We demonstrate that expression of |31-integrin increases in EZCs following SCI in mice. Conditional knock-out of /31-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of |31-integrin from EZCs in vivo reduced the number of EZC progeny that continued to express stem cell markers after SCI, increased the proportion of EZCprogeny that differentiated into GFAP + astrocytes, and diminished functional recovery. Loss of /31-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that /31-integrin directly interacts with the bone morphogenetic protein receptor sub-units BMPR1a and BMPR1b. Ablation of/31-integrin reduced overall levels of BMP receptors but significantly increased partitioning of BMPR1b into lipid rafts with increased SMAD1/5/8 and p38 signaling. Thus /31-integrin expression by EZCs reduces movement of BMPR1b into lipid rafts, thereby limiting the known deleterious effects of BMPR1b signaling on glial scar formation after SCI.