Development of oculomotor circuitry independent of hox3 genes

Abstract

Hox genes have been shown to be essential in vertebrate neural circuit formation and their depletion has resulted in homeotic transformations with neuron loss and miswiring. Here we quantifiy four eye movements in the zebrafish mutant valentino and hox3 knockdowns and find that contrary to the classical model, oculomotor circuits in hindbrain rhombomeres 5-6 develop and function independently from hox3 genes. All subgroups of oculomotor neurons are present as well as their input and output connections. Ectopic connections are also established, targeting two specific subsets of horizontal neurons and the resultant novel eye movements coexist with baseline behaviors. We conclude that the high expression of hox3 genes in rhombomeres 5-6 serves to prevent an aberrant neuronal identity and behaviors, but does not appear to be necessary for a comprehensive assembly of functional oculomotor circuits.

Key Features of Structural and Functional Organization of Zebrafish Facial Motor Neurons Are Resilient to Disruption of Neuronal Migration

“…Others have used genetic manipulation of hindbrain patterning genes to provide some evidence of flexibility and robustness in the developmental program, by studying the functional properties of ectopically induced neurons [32,33] and populations developing in the absence of normal segmental gene expression [34]. Indeed, a previous study in mice [35] provided indirect evidence that a mutation blocking FBMN caudal migration also extended the rostrocaudal range of the embryonic parafacial oscillator (e-pF) and spared specific features of respiratory connectivity.…”

“…In addition, even when circuits achieve their normal function despite some developmental perturbation, they may be vulnerable to dysfunction in specific contexts. For example, Ma et al [34] found that disruption of normal segmental gene expression in valentino zebrafish mutants resulted in sporadic, aberrant oculomotor behaviors (correlated with jaw and fin movements) layered on top of normal horizontal eye movements. The authors concluded that normal segmental signaling may protect developing circuits from aberrant connectivity.…”

“…Others have noted that these phylogenetic shifts in position seem to correlate with changes in function: in species where FBMNs receive strong inputs from caudal hindbrain networks (like respiratory central pattern generators), FBMNs migrate and settle in more caudal positions [8–11]. Adjusting the extent of neuronal migration to shift FBMNs closer to the source of their predominant synaptic inputs could be adaptive, by minimizing the total length of projections – in accord with the notion of wiring minimization [40,41] – or by adjusting the probability or strength of synaptic connections without specifying them in a deterministic fashion (as suggested by [34]). These selective forces (and possibly others) may act in tandem to confer an adaptive advantage on one settling location over another in a particular species.…”

Electron Microscopic Reconstruction of Functionally Identified Cells in a Neural Integrator

“…To locate the border between r6 and r7 we followed a similar approach that was performed previous using light microscopic imaging and the expression of the hox genes [55, 49, 29]. Briefly reticulospinal cells were identified based on the ultrastructure, that was very different form the remaining cells in the area.…”

Sustained Rhythmic Brain Activity Underlies Visual Motion Perception in Zebrafish

“…Halorhodopsin was locally activated via a 565 nm light-emitting diode (LED) coupled to a 100 μm optic fiber (Figure 2A; Supplemental Experimental Procedures) that was positioned unilaterally roughly above rhombomere 5, which was previously found to affect directional saccade generation in zebrafish when optogenetically inhibited (Schoonheim et al., 2010). This location likely corresponds to the nucleus abducens (Ma et al., 2014). …”