Dolphin, N. M. | bioRxiv Science

bioRxiv2025

GnRH-1 Neurons Are Not in the Goofy Group: 123cre Tracing Sets the Record Straight

The olfactory placode (OP) gives rise to a wide array of chemosensory neurons in the nasal region, including olfactory sensory neurons, vomeronasal sensory neurons, and those of the septal organ and Grueneberg ganglion. During placodal invagination, the OP also produces migratory neurons, including gonadotropin-releasing hormone-1 (GnRH-1) neurons, somatostatin-expressing neurons, Prokineticin Receptor 2 (Prokr2) pioneer/terminal nerve (TN) neurons, which are thought to initiate olfactory bulb development. Despite decades of research, the genetic lineage and molecular identity of OP-derived neuronal types remain under investigation. GnRH-1 neurons play essential roles in reproduction and chemodetection but appear genetically distinct from olfactory and vomeronasal chemosensory neurons. The Golgi-associated olfactory signaling regulator Goofy/Gfy is broadly expressed across the placode-derived nasal chemosensory neurons. To determine whether its expression is specific to nasal chemosensory neurons or it is a shared genetic feature across OP derivatives we characterized Gfy expression and lineage at embryonic and postnatal stages. Our results confirm broad Gfy expression in developing chemosensory neurons and subsets of olfactory pioneer/TN neurons. However, we found that while Gfy was not expressed in GnRH-1 neurons while migrating, analysis at late development and postnatal stages, revealed the existence of Gfy-traced neuronal populations in the basal forebrain, some of which also express GnRH. These findings uncover previously unrecognized genetic heterogeneity among migratory nasal neurons and reinforce previous studies suggesting the existence of additional neurons with nasal origin in the brain. In addition to this, analysis of Gfy expression along the developmental trajectory of vomeronasal sensory neurons at postnatal stages revealed intriguing differences in the developmental dynamics across the two main types of vomeronasal sensory neurons.

developmental biology↗

bioRxiv2023

Following the p63/Keratin5 Basal Cells in the Sensory and Non-sensory Epithelia of The Vomeronasal Organ

The Vomeronasal organ (VNO) is a part of the accessory olfactory system, which is responsible for detecting pheromones, chemical factors that trigger a spectrum of sexual and social behaviors. The vomeronasal epithelium (VNE) shares several features with the epithelium of the main olfactory epithelium (MOE). However, it is a distinct neuroepithelium populated by chemosensory neurons that differ from the olfactory sensory neurons (OSNs) in cellular structure, receptor expression, and connectivity. The vomeronasal organ of rodents comprises a sensory epithelium and a thin non-sensory epithelium that morphologically resembles the respiratory epithelium. Sox2-positive cells have been previously identified as the stem cell population that gives rise to neuronal progenitors in MOE and VNE. In addition to these, the MOE also comprises p63 positive horizontal basal cells (HBCs), a second pool of quiescent stem cells that become active in response to injury. Immunolabeling against the transcription factor p63, Keratin-5 (Krt5), Krt14 and Krt5Cre tracing experiments highlighted the existence of horizontal basal cells distributed along the basal lamina of the VNO forming from progenitors along the basal lamina of the marginal zones. Moreover, these experiments revealed that the NSE of rodents is, like the respiratory epithelium, a stratified epithelium where the p63/Krt5+ basal cells self-replicate and give rise to the apical columnar cells facing the lumen of the VNO.

developmental biology↗