{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:18:48Z","timestamp":1760660328038,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NINDS","award":["R01 NS128053"],"award-info":[{"award-number":["R01 NS128053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The primary cilium is generally viewed as a sensory organelle that transduces chemical and mechanical stimuli from the environment. In the adult hippocampus, primary cilia mediate the effects of sonic hedgehog (Shh) and other signals on neurogenesis and hippocampal function, and loss of cilia leads to cognitive and behavioral deficits. The secreted peptide noggin is a bone morphogenetic protein (BMP) antagonist and plays a critical role in regulating adult hippocampal neurogenesis (AHN) and hippocampus-dependent behavior. Here, 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.<\/jats:p>","DOI":"10.3390\/cells14201607","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:17:02Z","timestamp":1760617022000},"page":"1607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuronal Primary Cilia Mediate Noggin Release to Enable Extracellular Signaling"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5072-8376","authenticated-orcid":false,"given":"Sara R.","family":"Dunlop","sequence":"first","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-1410","authenticated-orcid":false,"given":"Justin A.","family":"Geier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-0894","authenticated-orcid":false,"given":"Chian-Yu","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-7712","authenticated-orcid":false,"given":"John A.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10401","DOI":"10.1523\/JNEUROSCI.2144-18.2018","article-title":"Adult Hippocampal Neurogenesis: A Coming-of-Age Story","volume":"38","author":"Kuhn","year":"2018","journal-title":"J. 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