Fate-Mapping the Mammalian Hindbrain: Segmental Origins of Vestibular Projection Neurons Assessed Using Rhombomere-SpecificHoxa2Enhancer Elements in the Mouse Embryo

Abstract

As a step toward generating a fate map of identified neuron populations in the mammalian hindbrain, we assessed the contributions of individual rhombomeres to the vestibular nuclear complex, a major sensorimotor area that spans the entire rhombencephalon. Transgenic mice harboring either the lacZ or the enhanced green fluorescent protein reporter genes under the transcriptional control of rhombomere-specific Hoxa2 enhancer elements were used to visualize rhombomere-derived domains. We labeled functionally identifiable vestibular projection neuron groups retrogradely with conjugated dextran-amines at successive embryonic stages and obtained developmental fate maps through direct comparison with the rhombomere-derived domains in the same embryos. The fate maps show that each vestibular neuron group derives from a unique rostrocaudal domain that is relatively stable developmentally, suggesting that anteroposterior migration is not a major contributor to the rostrocaudal patterning of the vestibular system. Most of the groups are multisegmental in origin, and each rhombomere is fated to give rise to two or more vestibular projection neuron types, in a complex pattern that is not segmentally iterated. Comparison with studies in the chicken embryo shows that the rostrocaudal patterning of identified vestibular projection neuron groups is generally well conserved between avians and mammalians but that significant speciesspecific differences exist in the rostrocaudal limits of particular groups. This mammalian hindbrain fate map can be used as the basis for targeting genetic manipulation to specific subpopulations of vestibular projection neurons.

Connecting Ears to Eye Muscles: Evolution of a ‘Simple' Reflex Arc

“…2 a), a pattern that is conserved from frogs to mammals [Glover and Petursdottir, 1991;Suwa et al, 1996;Glover, 2000;Straka et al, 2001;Pasqualetti et al, 2007]. Vestibulo-ocular projections derive from a larger number of groups ( fig.…”

“…2 ). Vestibulospinal projection neurons in fish, frog , chicken [Glover and Petursdottir, 1991; and mouse [Pasqualetti et al, 2007] are known to be nearly completely distinct from those giving rise to vestibuloocular or vestibulocerebellar projections, with only a small subgroup projecting to both spinal and oculomotor targets ( fig. 2 c) .…”

“…Thus, studies linking gene expression patterns to connectivity patterns are leading to a reclassification of vestibular anatomy that more clearly reflects the developmental and evolutionary processes responsible for its formation and ultimate function. Indeed, on this hodological backdrop, species-specific variants can be seen that obviously represent selections for or against specific elements of the presumptive vertebrate blueprint [Díaz and Glover, 2002;Pasqualetti et al, 2007;Straka and Baker, 2013].…”

The emerging framework of mammalian auditory hindbrain development

“…Single rhombomeres can therefore contribute to distinct neuronal systems. On the other hand, neuronal groups can be composed of cells, originating from different rhombomeres (Tan and Le Douarin 1991;Marin and Puelles 1995;Cramer et al 2000;Farago et al 2006;Di Bonito et al 2013b;Pasqualetti et al 2007) (Fig. 2).…”

Functional Development of the Vestibular System

“…Each vestibular functional group is derived from a unique rostrocaudal domain (Pasqualetti et al, 2007). Different vestibular populations are segregated by E14.5, and their establishment is definitively achieved at E16.5 (Auclair et al, 1999;Pasqualetti et al, 2007) (Figs.…”