Abstract
ABSTRACTThe 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 β (TGFβ) 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 TGFβ/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.
Highlights
Neurons form complex and conserved neuronal circuits by innervating the dendritic compartments of specific target neurons
Localization of active bone morphogenetic protein (BMP) signaling in basal vomeronasal sensory neurons (VSNs) We analyzed mRNA-seq data from postnatal vomeronasal organ (VNO) (GSE134492) and found that the vomeronasal epithelium (VNE) expresses multiple molecules of the BMP/ transforming growth factor β (TGFβ) family
Our study shows that canonical BMP signaling is necessary for maturation of functional basal VSNs and for their circuit formation with the accessory olfactory bulb (AOB)
Summary
Neurons form complex and conserved neuronal circuits by innervating the dendritic compartments of specific target neurons. The vomeronasal organ (VNO) is a specialized vertebrate olfactory subsystem used to detect pheromones (Cloutier et al, 2002; Dulac, 2000; Isogai et al, 2011; Mombaerts et al, 1996). Neurons of the vomeronasal epithelium (VNE) continue to form postnatally (de la Rosa-Prieto et al, 2010). As newly formed neurons mature, they innervate dendrites of specific second-order neurons in the accessory olfactory bulb (AOB) (Mombaerts et al, 1996). The sensory epithelium of the mouse VNO is composed of Department of Biological Sciences; The RNA Institute; University at Albany, State University of New York, Albany, NY 12222, USA
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