Identifying Isl1 genetic lineage in the developing olfactory system and in GnRH-1 neurons

Abstract

During embryonic development, symmetric ectodermal thickenings (olfactory placodes) give rise to several cell types that comprise the olfactory system, such as those that form the terminal nerve ganglion (TN), gonadotropin releasing hormone-1 (GnRH-1) neurons and other migratory neurons in rodents. Even though the genetic heterogeneity among these cell types are documented, unidentified cell populations arising from the olfactory placode remain. One candidate to identify placodal derived neurons in the developing nasal area is the transcription factor Isl1, which was recently identified in GnRH-3 neurons of the terminal nerve in fish, as well as expression in neurons of the nasal migratory mass. Here, we analyzed the Isl1 genetic lineage in chemosensory neuronal populations in the nasal area and migratory GnRH-1 neurons in mice using in-situ hybridization, immunolabeling a Tamoxifen inducible Isl1CreERT and a constitutive Isl1Cre knock-in mouse lines. In addition, we also performed conditional Isl1 ablation in developing GnRH neurons. We found Isl1 lineage across non sensory cells of the respiratory epithelium and sustentacular cells of OE and VNO. We identified a population of transient embryonic Isl1+ neurons in the olfactory epithelium and sparse Isl1+ neurons in postnatal VNO. Isl1 is expressed in almost all GnRH neurons and in approximately half of the other neuron populations in the Migratory Mass. However, Isl1 conditional ablation alone does not significantly compromise GnRH-1 neuronal migration or GnRH-1 expression, suggesting compensatory mechanisms. Further studies will elucidate the functional and mechanistic role of Isl1 in development of migratory endocrine neurons.

Lineage, Identity, and Fate of Distinct Progenitor Populations in the Embryonic Olfactory Epithelium

“…We used conditional recombination of a reporter to identify temporally distinct, lineally-related subsets of Ascl1+ OE precursors (Cau et al, 2002; Cau et al, 1997; Guillemot et al, 1993; Murray et al, 2003; Tucker et al, 2010) shortly after the initial OE morphogenesis. Similar approaches have been used to assess temporally discrete populations of Ascl1+ precursors in the spinal cord, cerebellum, and cerebral cortex (Allaway et al, 2020; Battiste et al, 2007; Sudarov et al, 2011; Vue et al, 2014) as well as for Isl1+ OE precursor fates (Taroc et al, 2020). The central role suggested for Ascl1 and other neurogenic genes in olfactory pathway development (Cau et al, 2002; Guillemot et al, 1993; Murray et al, 2003) led us to these experiments focused on Ascl1+ OE cells at the earliest stages of olfactory pathway differentiation.…”

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

“…We performed GFP/Meis2/HUCD triple immunofluorescence to distinguish among sustentacular cells and, apical and basal VSNs in the NICD inducible pups. As HUCD is only expressed in neuronal population [41], we considered Meis2+/HUCD-as non-neuronal sustentacular cells, Meis2+/HUCD+ as apical VSNs and Meis2-/HUCD+ as basal VSNs. The analysis in the inducible mice showed that 66.6% of the NICD: EGFP population became sustentacular and only 32.3% of the recombined cells were found to be VSNs (Fig.…”