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Homeobox genes and the specification of neuronal identity

Nature Reviews Neuroscience volume 22, pages 627–636 (2021)Cite this article

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Abstract

The enormous diversity of cell types that characterizes any animal nervous system is defined by neuron-type-specific gene batteries that endow cells with distinct anatomical and functional properties. To understand how such cellular diversity is genetically specified, one needs to understand the gene regulatory programmes that control the expression of cell-type-specific gene batteries. The small nervous system of the nematode Caenorhabditis elegans has been comprehensively mapped at the cellular and molecular levels, which has enabled extensive, nervous system-wide explorations into whether there are common underlying mechanisms that specify neuronal cell-type diversity. One principle that emerged from these studies is that transcription factors termed ‘terminal selectors’ coordinate the expression of individual members of neuron-type-specific gene batteries, thereby assigning unique identities to individual neuron types. Systematic mutant analyses and recent nervous system-wide expression analyses have revealed that one transcription factor family, the homeobox gene family, is broadly used throughout the entire C. elegans nervous system to specify neuronal identity as terminal selectors. I propose that the preponderance of homeobox genes in neuronal identity control is a reflection of an evolutionary trajectory in which an ancestral neuron type was specified by one or more ancestral homeobox genes, and that this functional linkage then duplicated and diversified to generate distinct cell types in an evolving nervous system.

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Fig. 1: Homeobox gene complement in some model animal genomes.
Fig. 2: Models for the regulation of neuron-type-specific gene batteries by transcription factors.
Fig. 3: Homeobox gene expression in the nervous system of Caenorhabditis elegans.
Fig. 4: Terminal selectors in Caenorhabditis elegans.
Fig. 5: A hypothetical scenario for the individuation of two sister neurons.

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Acknowledgements

The author thanks M. Reilly for help with the figures, M. Tosches, T. Bürglin, P. Kratsios and the current members of his laboratory for comments on the manuscript and the Howard Hughes Medical Institute for funding.

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  1. Department of Biological Sciences, Columbia University, Howard Hughes Medical Institute, New York, NY, USA

    Oliver Hobert

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Nature Reviews Neuroscience thanks K. Lee, who co-reviewed with C. Doe, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Hobert, O. Homeobox genes and the specification of neuronal identity. Nat Rev Neurosci 22, 627–636 (2021). https://doi.org/10.1038/s41583-021-00497-x

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