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Phenotypes

Mouse phenotype:

abnormal heart morphology, abnormal neural tube closure, abnormal kidney morphology, small kidney, abnormal embryo turning

Subcellular localization

basal body

Functional category

• Non-motile cilium / primary cilium

Function

We show that noggin is expressed by mature granule cell neurons, that it is apically targeted and localized intracellularly near the pocket region of primary cilia, and that cilia regulate noggin release through Shh and somatostatin (SST) pathways. Further, granule cell activation modulates noggin dynamics both in vitro and in vivo. Together, these findings demonstrate synergy between Shh and noggin and the positive regulatory action of neuronal activity on regulating BMP antagonism within the neurogenic niche. Thus, the primary cilium is not only an organelle that transduces signals to neurons but also one that mediates extracellular signaling. Significance statement: Primary cilia are organelles that protrude from the surface of most vertebrate cell types. Defects in primary ciliary structure and function are associated with human disease. Primary cilia are generally viewed as exclusively sensory organelles that respond to environmental signals to regulate both cell development and adult cell function. This study demonstrates that the primary cilia in hippocampal granule cell neurons mediate the release of the BMP antagonist, noggin. These observations expand the current understanding of ciliary signaling and may inform future studies exploring the connection between hippocampal activity and cognition in ciliopathies(41148821).