YAP and TAZ loss of function in the neural crest broadly affects olfactory ensheathing cells, olfactory-vomeronasal neurons, but not GnRH-1 neuronal migration.
Olfactory Ensheathing Cells (OECs) originate from the neural crest and are critical for bundling olfactory axons to the brain. Their development is vital for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs are of particular interest for potential treatments of central nervous system lesions, though their development is not fully understood. Our single-cell RNA sequencing of mouse embryonic nasal tissues suggests that OECs and Schwann cells share a common origin from Schwann Cell Precursors (SCPs). However, OECs and SCs have significant genetic differences. Wnt1 is highly expressed in pre-migratory neural crest cells, while Sox10 expression occurs later and is lost in most derivatives, except for nasal cartilage, SCPs, SCs, melanocytes, and OECs. Rosa26 lineage tracing revealed that the Wnt1Cre2 mouse line recombines extensively in non-neural crest-derived tissues, while Sox10 Cre more selectively recombines in neural crest derivatives. We used Sox10 Cre mice to manipulate the Yap and Taz genes in migrating neural crest cells. Our analyses showed reduced Sox10+ cells in the nasal region and alterations in gene expression of SCs, melanocytes, and OECs. However, GnRH-1 neuronal migration remained unaffected. Notably, the loss of Yap and Taz in neural crest derivatives led to significant secondary effects in olfactory structures, reducing both olfactory sensory neurons and vascularization in the vomeronasal organ (VNO). Our findings highlight the importance of the Hippo pathway in OEC development and its implications for the olfactory vasculature. Overall design: Whole embryonic noses were dissected from E14.5 yap flox/flox;taz flox/flox and Sox10cre;yap flox/WT;taz flox/flox mice, cells were isolated then analyzed using scRNAseq.