Notch signaling determines cell-fate specification of the two main types of vomeronasal neurons of rodents

Abstract

The ability of terrestrial vertebrates to find food and mating partners, and to avoid predators, relies on the detection of chemosensory information. Semiochemicals responsible for social and sexual behaviors are detected by chemosensory neurons of the vomeronasal organ (VNO), which transmits information to the accessory olfactory bulb. The vomeronasal sensory epithelium of most mammalian species contains a uniform vomeronasal system; however, rodents and marsupials have developed a more complex binary vomeronasal system, containing vomeronasal sensory neurons (VSNs) expressing receptors of either the V1R or V2R family. In rodents, V1R/apical and V2R/basal VSNs originate from a common pool of progenitors. Using single cell RNA-sequencing, we identified differential expression of Notch1 receptor and Dll4 ligand between the neuronal precursors at the VSN differentiation dichotomy. Our experiments show that Notch signaling is required for effective differentiation of V2R/basal VSNs. In fact, Notch1 loss of function in neuronal progenitors diverts them to the V1R/apical fate, whereas Notch1 gain of function redirects precursors to V2R/basal. Our results indicate that Notch signaling plays a pivotal role in triggering the binary differentiation dichotomy in the VNO of rodents.

Sociosexual behavior requires both activating and repressive roles of Tfap2e/AP- 2ε in vomeronasal sensory neurons

“…These also express Gnai2/ Gαi2, Nrp2 and V1rs at more mature stages (Figure 1I-K). On the other side, mRNA for the transcription factors Tfap2e/AP-2ε (Figure 1K) was found to be expressed, in line with our prior works (Katreddi et al, 2022; Lin et al, 2018), in differentiating/maturing and mature basal VSNs. The basal VSNs’ differentiation trajectory was further confirmed by the expression of known V2r/basal VSNs’ markers such as Robo2, Gnao1/Gαo, and Vnm2r receptors (Figure 1K-N).…”

“…These also express Gnai2/ Gai2, Nrp2 and V1rs at more mature stages (Figure 1I-K). On the other side, mRNA for the transcription factors Tfap2e/AP-2e (Figure 1K) was found to be expressed, in line with our prior works (Katreddi et al, 2022;Lin et al, 2018), in differentiating/maturing and mature basal VSNs.…”

“…Consistent with prior reports, the mRNA for the transcription factor Bcl11b (Figure 1F) was found to be expressed in Neurog1+/NeuroD1+ (Figure 1B,C) precursors and in differentiating apical and basal VSNs. While Bcl11b was expressed as a continuum along the basal differentiation trajectory, in the apical neurons, Bcl11b was not expressed until later stages of maturation (Figure 1F) (Enomoto et al, 2011; Katreddi et al, 2022). The transcription factor Meis2 was expressed in progenitor cells as well as in apical VSNs’ differentiating neurons (Figure 1G).…”

“…The scRNA-seq data discussed in this publication have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO series accession number GSE192746 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192746). We also utilized previously published data from (Katreddi et al, 2022), available through GEO series accession number GSE190330 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190330).…”

“…(https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE192746). We also utilized previously published data from (Katreddi et al, 2022), available through GEO series accession number GSE190330…”