Abstract
A remarkable diversity of cell types characterizes every animal nervous system. Previous studies provided important insights into how neurons commit to a particular fate, migrate to the right place and form precise axodendritic patterns. However, the mechanisms controlling later steps of neuronal development remain poorly understood. Hox proteins represent a conserved family of homeodomain transcription factors with well-established roles in anterior-posterior (A-P) patterning and the early steps of nervous system development, including progenitor cell specification, neuronal migration, cell survival, axon guidance and dendrite morphogenesis. This review highlights recent studies in Caenorhabditis elegans, Drosophila melanogaster and mice that suggest new roles for Hox proteins in processes occurring during later steps of neuronal development, such as synapse formation and acquisition of neuronal terminal identity features (e.g., expression of ion channels, neurotransmitter receptors, and neuropeptides). Moreover, we focus on exciting findings suggesting Hox proteins are required to maintain synaptic structures and neuronal terminal identity during post-embryonic life. Altogether, these studies, in three model systems, support the hypothesis that certain Hox proteins are continuously required, from early development throughout post-embryonic life, to build and maintain a functional nervous system, significantly expanding their functional repertoire beyond the control of early A-P patterning.
Highlights
Nervous system development is a multi-step process that generates a multitude of cell types
Split GFP reporter technology (GRASP) revealed that the DA9 synaptic input fails to be maintained in adult egl-5 mutants, despite being properly established at earlier larval stages, indicating a critical role for egl-5 in synapse maintenance. These findings suggest that the posterior Hox gene egl-5 controls both synaptic input and output of a posterior cholinergic motor neuron (DA9) in C. elegans
The maintained Hox expression in the mouse hindbrain and spinal cord prompts the question of what are the biological functions of mouse Hox genes in post-mitotic neurons during late developmental and postnatal stages? Below, we highlight studies on the role of mouse Hox genes in synapse formation/maturation and neuronal terminal identity; these lateoccurring processes critically determine the functionality of neural circuits located in the hindbrain and spinal cord (Table 1)
Summary
Nervous system development is a multi-step process that generates a multitude of cell types. Recent studies on two different neuron types in C. elegans, namely the touch receptors and nerve cord motor neurons, revealed a new role for Hox genes in the control of neuronal terminal identity (Table 1). These studies proposed that CEH-13 and EGL5 function as transcriptional guarantors by controlling the levels of expression of the terminal selector gene mec-3, which in turn is required for terminal identity of both ALM and PLM neurons (Figure 1C; Zheng et al, 2015a,b).
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