Abstract
Unraveling the inner workings of neural circuits entails understanding the cellular origin and axonal pathfinding of various neuronal groups during development. In the embryonic hindbrain, different subtypes of dorsal interneurons (dINs) evolve along the dorsal-ventral (DV) axis of rhombomeres and are imperative for the assembly of central brainstem circuits. dINs are divided into two classes, class A and class B, each containing four neuronal subgroups (dA1-4 and dB1-4) that are born in well-defined DV positions. While all interneurons belonging to class A express the transcription factor Olig3 and become excitatory, all class B interneurons express the transcription factor Lbx1 but are diverse in their excitatory or inhibitory fate. Moreover, within every class, each interneuron subtype displays its own specification genes and axonal projection patterns which are required to govern the stage-by-stage assembly of their connectivity toward their target sites. Remarkably, despite the similar genetic landmark of each dINs subgroup along the anterior-posterior (AP) axis of the hindbrain, genetic fate maps of some dA/dB neuronal subtypes uncovered their contribution to different nuclei centers in relation to their rhombomeric origin. Thus, DV and AP positional information has to be orchestrated in each dA/dB subpopulation to form distinct neuronal circuits in the hindbrain. Over the span of several decades, different axonal routes have been well-documented to dynamically emerge and grow throughout the hindbrain DV and AP positions. Yet, the genetic link between these distinct axonal bundles and their neuronal origin is not fully clear. In this study, we reviewed the available data regarding the association between the specification of early-born dorsal interneuron subpopulations in the hindbrain and their axonal circuitry development and fate, as well as the present existing knowledge on molecular effectors underlying the process of axonal growth.
Highlights
The vertebrate central nervous system (CNS) is composed of a vast array of neuronal circuits that are assembled in a stepwise manner to give rise to the enormous diversity of cells and functions
Many studies uncovered genes that regulate different aspects of the multi-event process that spans from neural specification to circuit formation, there is still missing knowledge regarding how these complex mechanisms are orchestrated to give rise to functional networks, and what goes wrong in neurodevelopmental disorders
Two more ascending ipsilateral projections were evident; one emerged from a medial position forming an ipsilateral funiculus (LF) whereas the other elongated in a dorsal position forming an ipsi dorsal funiculus (DF) (Figure 5A). These axons projected and terminated in the medulla, cerebellum, mesencephalicus lateralis pars dorsalis (MLD), and EW nuclei, invariably with the above-mentioned axonal routes of the vestibular and auditory nuclei (Figures 5B,C). These findings enabled us to connect the dB1 lineage with typical hindbrain tracts and target sites, as well as to uncover that dB1 axons begin to project toward different targets before their cell body migrate and settle in their final VN/cochlear nuclei (CN) centers (Kohl et al, 2015)
Summary
The vertebrate central nervous system (CNS) is composed of a vast array of neuronal circuits that are assembled in a stepwise manner to give rise to the enormous diversity of cells and functions. Advanced combinations of axonal labeling in knockout or reporter mice lines enabled to link Phox2b+ neurons in the NTS with these circuits (Qian et al, 2001; Dauger et al, 2003; Pattyn et al, 2006; Sieber et al, 2007; Smith et al, 2009; Storm et al, 2009; Hernandez-Miranda et al, 2017), tracking the gradual axonal growth of distinct dA3 INs before and after populating different subdomains along the NTS is missing Unraveling this issue is important since the NTS contains diverse intermingled subpopulations of neurons that modulate distinct functions by their extensive projections. Further studies are required to elucidate FMRP-downstream RNA targets in dA1 axons and to uncover whether fragile X patients suffer from axonal development deficits in the auditory brainstem
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
