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 beta 1-integrin increases in EZCs following SCI in mice. Conditional knock-out of beta 1-integrin increases GFAP expression and astrocytic differentiation by cultured EZCs without altering oligodendroglial or neuronal differentiation. Ablation of beta 1-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 intoGFAP + astrocytes, and diminished functional recovery. Loss of beta 1-integrin increased SMAD1/5/8 and p38 signaling, suggesting activation of BMP signaling. Coimmunoprecipitation studies demonstrated that beta 1-integrin directly interacts with the bone morphogenetic protein receptor sub-units BMPR1a and BMPR1b. Ablation of beta 1-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 beta 1-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.