PMID- 32341026 OWN - NLM STAT- MEDLINE DCOM- 20201216 LR - 20201216 IS - 1477-9129 (Electronic) IS - 0950-1991 (Print) IS - 0950-1991 (Linking) VI - 147 IP - 8 DP - 2020 Apr 27 TI - Smad4-dependent morphogenic signals control the maturation and axonal targeting of basal vomeronasal sensory neurons to the accessory olfactory bulb. LID - 10.1242/dev.184036 [doi] LID - dev184036 AB - The vomeronasal organ (VNO) contains two main types of vomeronasal sensory neurons (VSNs) that express distinct vomeronasal receptor (VR) genes and localize to specific regions of the neuroepithelium. Morphogenic signals are crucial in defining neuronal identity and network formation; however, if and what signals control maturation and homeostasis of VSNs is largely unexplored. Here, we found transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) signal transduction in postnatal mice, with BMP signaling being restricted to basal VSNs and at the marginal zones of the VNO: the site of neurogenesis. Using different Smad4 conditional knockout mouse models, we disrupted canonical TGFbeta/BMP signaling in either maturing basal VSNs (bVSNs) or all mature VSNs. Smad4 loss of function in immature bVSNs compromises dendritic knob formation, pheromone induced activation, correct glomeruli formation in the accessory olfactory bulb (AOB) and survival. However, Smad4 loss of function in all mature VSNs only compromises correct glomeruli formation in the posterior AOB. Our results indicate that Smad4-mediated signaling drives the functional maturation and connectivity of basal VSNs. CI - (c) 2020. Published by The Company of Biologists Ltd. FAU - Naik, Ankana S AU - Naik AS AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Lin, Jennifer M AU - Lin JM AUID- ORCID: 0000-0002-9197-0816 AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Taroc, Ed Zandro M AU - Taroc EZM AUID- ORCID: 0000-0002-0873-4901 AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Katreddi, Raghu R AU - Katreddi RR AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Frias, Jesus A AU - Frias JA AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Lemus, Alex A AU - Lemus AA AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Sammons, Morgan A AU - Sammons MA AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA. FAU - Forni, Paolo E AU - Forni PE AUID- ORCID: 0000-0001-6547-3464 AD - Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA pforni@albany.edu. LA - eng GR - R01 DC017149/DC/NIDCD NIH HHS/United States GR - R01 HD097331/HD/NICHD NIH HHS/United States GR - R15 GM128049/GM/NIGMS NIH HHS/United States GR - R15 HD096411/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200427 PL - England TA - Development JT - Development (Cambridge, England) JID - 8701744 RN - 0 (Bone Morphogenetic Proteins) RN - 0 (GAP-43 Protein) RN - 0 (Smad4 Protein) RN - 0 (Transforming Growth Factor beta) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Animals MH - Axons/*metabolism MH - Bone Morphogenetic Proteins/metabolism MH - Dendrites/metabolism MH - GAP-43 Protein/metabolism MH - Gene Deletion MH - Integrases/metabolism MH - Mice, Knockout MH - *Morphogenesis MH - Odorants MH - Olfactory Bulb/*metabolism MH - Presynaptic Terminals/metabolism MH - Sensory Receptor Cells/*metabolism MH - Signal Transduction MH - Smad4 Protein/*metabolism MH - Transcriptome/genetics MH - Transforming Growth Factor beta/metabolism MH - Vomeronasal Organ/*metabolism PMC - PMC7197725 OTO - NOTNLM OT - Axonal targeting OT - BMP OT - Glomeruli OT - Olfactory OT - Smad4 OT - Vomeronasal sensory neurons COIS- Competing interestsThe authors declare no competing or financial interests. EDAT- 2020/04/29 06:00 MHDA- 2020/12/17 06:00 PMCR- 2020/04/27 CRDT- 2020/04/29 06:00 PHST- 2019/08/20 00:00 [received] PHST- 2020/03/10 00:00 [accepted] PHST- 2020/04/29 06:00 [entrez] PHST- 2020/04/29 06:00 [pubmed] PHST- 2020/12/17 06:00 [medline] PHST- 2020/04/27 00:00 [pmc-release] AID - 147/8/dev184036 [pii] AID - DEV184036 [pii] AID - 10.1242/dev.184036 [doi] PST - epublish SO - Development. 2020 Apr 27;147(8):dev184036. doi: 10.1242/dev.184036.