The emergence of mesencephalic trigeminal neurons

Abstract

BackgroundThe cells of the mesencephalic trigeminal nucleus (MTN) are the proprioceptive sensory neurons that innervate the jaw closing muscles. These cells differentiate close to the two key signalling centres that influence the dorsal midbrain, the isthmus, which mediates its effects via FGF and WNT signalling and the roof plate, which is a major source of BMP signalling as well as WNT signalling.MethodsIn this study, we have set out to analyse the importance of FGF, WNT and BMP signalling for the development of the MTN. We have employed pharmacological inhibitors of these pathways in explant cultures as well as utilising the electroporation of inhibitory constructs in vivo in the chick embryo.ResultsWe find that interfering with either FGF or WNT signalling has pronounced effects on MTN development whilst abrogation of BMP signalling has no effect. We show that treatment of explants with either FGF or WNT antagonists results in the generation of fewer MTN neurons and affects MTN axon extension and that inhibition of both these pathways has an additive effect. To complement these studies, we have used in vivo electroporation to inhibit BMP, FGF and WNT signalling within dorsal midbrain cells prior to, and during, their differentiation as MTN neurons. Again, we find that inhibition of BMP signalling has no effect on the development of MTN neurons. We additionally find that cells electroporated with inhibitory constructs for either FGF or WNT signalling can differentiate as MTN neurons suggesting that these pathways are not required cell intrinsically for the emergence of these neurons. Indeed, we also show that explants of dorsal mesencephalon lacking both the isthmus and roof plate can generate MTN neurons. However, we did find that inhibiting FGF or WNT signalling had consequences for MTN differentiation.ConclusionsOur results suggest that the emergence of MTN neurons is an intrinsic property of the dorsal mesencephalon of gnathostomes, and that this population undergoes expansion, and maturation, along with the rest of the dorsal midbrain under the influence of FGF and WNT signalling.

Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice

“…DRG neurons, CSG neurons and MTNs are pseudo-unipolar primary afferent neurons, however, MTN are unique with respect to the localization of their cell bodies within the CNS. Whereas DRG and CSG are generated from neural crest cells or from transient focal thickenings of the ectoderm in the head region, MTN emerge from the dorsal mesencephalon and not from neural crest cells that invade the mesencephalon as previously thought (Hunter et al, 2001 ; Dyer et al, 2014 ; Lipovsek et al, 2017 ). In spite of their location in the CNS and their different origin, MTNs maintain some characteristics of other sensory neurons including the expression of Npr2 and cGKI and bifurcation of their afferent.…”

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

“…Brn3c is expressed in RGCs, nociceptors (Badea et al, 2012) and a subpopulation of proprioceptors (Oliver et al, 2020), and vestibulary and auditory hair cells (Xiang et al, 1997). We now describe Brn3c positive structures in the midbrain that include integration stations of sensory pathways, like the inferior colliculus, the intercollicular nucleus (Winer & Schreiner, 2005) and the deep layers of the SC as well as the mesencephalic trigeminal nucleus (containing proprioceptive neurons (Florez‐Paz, Bali, Kuner, & Gomis, 2016; Lipovsek et al, 2017)). Thus, Pou4f family members are repeatedly used in various stations of the sensory systems, offering an excellent example of evolutionary divergence of sensory circuits paralleled by expansions of transcription families dedicated to their specification (Hobert, 2011; Leyva‐Diaz, Masoudi, Serrano‐Saiz, Glenwinkel, & Hobert, 2020; Mao et al, 2016).…”

Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele

“…Brn3c is expressed in RGCs, nociceptors (T. C. Badea et al, 2012) and a subpopulation of proprioceptors (Oliver et al, 2020), and vestibulary and auditory hair cells (Xiang et al, 1997). We now describe Brn3c positive structures in the midbrain that include integration stations of sensory pathways, like the inferior colliculus, the intercollicular nucleus (Winer & Schreiner, 2005) and the deep layers of the superior colliculus as well as the mesencephalic trigeminal nucleus (containing proprioceptive neurons) (Florez- Paz, Bali, Kuner, & Gomis, 2016;Lipovsek et al, 2017). Thus Pou4f family members are repeatedly used in various stations of the sensory systems, offering an excellent example of evolutionary divergence of sensory circuits paralleled by expansions of transcription families dedicated to their specification (Hobert, 2011;Leyva-Diaz, Masoudi, Serrano-Saiz, Glenwinkel, & Hobert, 2020;Mao et al, 2016).…”