BMPR-2 gates activity-dependent stabilization of dendrites during mitral cell remodeling

Abstract

Developing neurons initially form excessive neurites and then remodel them based on molecular cues and neuronal activity. Developing mitral cells in the olfactory bulb initially extend multiple primary dendrites. They then stabilize single primary dendrites, while eliminating others. However, the mechanisms underlying the selective dendrite remodeling remain elusive. Using CRISPR/Cas9-based knockout screening combined with in utero electroporation, we identified BMPR-2 as a key regulator for the selective dendrite stabilization. Bmpr2 knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby facilitates dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicate that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we also demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of mitral cell dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.