Goofy/123Cre lineage tracing differentiates olfactory and vomeronasal neurons from GnRH-1 and terminal nerve neurons during neuronal migration and reveals additional olfactory placode-derived cells in the brain.

The olfactory placode (OP) generates a broad array of chemosensory neurons in the nasal region, including olfactory sensory neurons, vomeronasal sensory neurons, neurons of the septal organ, and Grueneberg ganglion. During invagination, the OP also generates migratory neuronal populations, including gonadotropin-releasing hormone-1 (GnRH-1) neurons, somatostatin-expressing neurons, and Prokineticin Receptor 2 (Prokr2) pioneer/terminal nerve (TN) neurons. Despite extensive research, the genetic lineage and molecular identity of many OP-derived neurons remain unclear. GnRH-1 neurons are vital for reproductive functions and chemosensory processing but are genetically distinct from olfactory and vomeronasal sensory neurons. The regulator Goofy/Gfy is expressed in placode-derived chemosensory neurons. Our study aimed to determine whether its expression is restricted to these neurons or shared among OP derivatives. The 123Cre mouse expresses Cre under the Gfy1 promoter. Cre tracing analyses across embryonic stages showed widespread 123Cre recombination in chemosensory neurons but not in migrating GnRH-1. However, at late development and postnatal stages, some Gfy-traced cells appear in the basal forebrain, including a subset of GnRH-positive neurons. These findings demonstrate heterogeneity among migratory nasal neurons and suggest that, besides GnRH-1, other nasal-origin neurons also populate the forebrain. Postnatal studies of vomeronasal neurons revealed distinct developmental trajectories for the two main VSN subtypes.