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

Cell Rep. 2021 Jun 22;35(12):109276. doi: 10.1016/j.celrep.2021.109276.


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 selective dendrite remodeling remain elusive. Using CRISPR-Cas9-based knockout screening combined with in utero electroporation, we identify BMPR-2 as a key regulator for selective dendrite stabilization. Bmpr2 knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby permits dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicates that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of primary dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.

Keywords: BMP; LIMK; NMDAR; Rac1; actin cytoskeleton; cofilin; dendrite remodeling; mitral cells; neuronal activity; olfactory bulb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Animals
  • Bone Morphogenetic Protein Receptors, Type II / chemistry
  • Bone Morphogenetic Protein Receptors, Type II / metabolism*
  • Bone Morphogenetic Proteins / metabolism
  • Dendrites / metabolism*
  • Glutamic Acid / metabolism
  • Ligands
  • Lim Kinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Olfactory Bulb / cytology*
  • Protein Domains
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Structure-Activity Relationship
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / metabolism


  • Actin Depolymerizing Factors
  • Actins
  • Bone Morphogenetic Proteins
  • Ligands
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Lim Kinases
  • Limk1 protein, mouse
  • p21-Activated Kinases
  • Bone Morphogenetic Protein Receptors, Type II
  • rac1 GTP-Binding Protein