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Annu Rev Cell Dev Biol,
2011]
The generation of individual neuron types in the nervous system is a multistep process whose endpoint is the expression of neuron type-specific batteries of terminal differentiation genes that determine the functional properties of a neuron. This review focuses on the regulatory mechanisms that are involved in controlling the terminally differentiated state of a neuron. I review several case studies from invertebrate and vertebrate nervous systems that reveal that many terminal differentiation features of a neuron are coregulated via terminal selector transcription factors that initiate and maintain terminal differentiation programs.
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Curr Biol,
2016]
We revisit the classification of neuronal cell types in the nervous system of the nematode Caenorhabditis elegans. Based on anatomy and synaptic connectivity patterns, the 302 neurons of the nervous system of the hermaphrodite were categorized into 118 neuron classes more than 30 years ago. Analysis of all presently available neuronal gene expression patterns reveals a remarkable congruence of anatomical and molecular classification and further suggests subclassification schemes. Transcription factor expression profiles alone are sufficient to uniquely classify more than 90% of all neuron classes in the C.elegans nervous system. Neuron classification in C.elegans may be paradigmatic for neuron classification schemes in vertebrate nervous systems.
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Dev Biol,
2019]
The shape of an individual neuron is linked to its function with axons sending signals to other cells and dendrites receiving them. Although much is known of the mechanisms for axonal outgrowth, the striking complexity of dendritic architecture has hindered efforts to uncover pathways that direct dendritic branching. Here we review the results of an experimental strategy that exploits the power of genetic analysis and live cell imaging of the PVD sensory neuron in C. elegans to reveal key molecular drivers of dendrite morphogenesis.
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Curr Biol,
2018]
Distinct neuronal cell types display phenotypic similarities such as their neurotransmitter identity. Studies inworms and flies have revealed that this phenotypic convergence can be brought about by distinct transcription factors regulating the same effector genes in different neuron types.
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Curr Opin Neurobiol,
2004]
Cellular diversity in the nervous system arises from the presence of multiple neuronal subtypes, each of which is specialized to perform a unique function. Work in Caenorhabditis elegans has begun to reveal the pathways that are essential for the specification of identities of neuronal subtypes in its chemosensory system. The functions of each chemosensory neuron subtype are specified by distinct developmental cascades, using molecules from well-conserved transcription factor families. Additional cellular complexity is generated by novel mechanisms that further diversify the identities of the left and right members of a bilateral sensory neuron pair.
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Annu Rev Genet,
1999]
Molecular genetic analysis of chemotaxis and theramotaxis in Caenorhabditis elegans has revealed the molecular bases of olfaction, taste, and thermosensation, which, in turn, has demonstrated that sensory signaling in C. elegans is very similar to that in vertebrates. A cyclic nucleotide-gated channel (TAX-2/TAX-4) that is highly homologous to the olfactory and photoreceptor channels in vertebrates is required for taste and thermosensation, in addition to olfaction. A cation channel (OSM-9) that is closely related to a capsaicin receptor channel is required for olfactory adaptation in one olfactory neuron and olfactory sensation in the other olfactory neuron. A novel G alpha protein (ODR-3) is essential for olfactory responses in all olfactory neurons and aversive responses in a polymodal sensory neuron. A G protein-coupled seven-transmembrane receptor (ODR-10) is the first olfactory receptor whose ligand was elucidated. Using chemotaxis and thermotaxis as behavioral paradigms, neural plasticity including learning and memory can be studied genetically in C. elegans.
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Curr Opin Neurobiol,
2019]
How do post-mitotic neurons acquire and maintain their terminal identity? Genetic mutant analysis in the nematode Caenorhabditis elegans has revealed common molecular programs that control neuronal identity. Neuron type-specific combinations of transcription factors, called terminal selectors, act as master regulatory factors to initiate and maintain terminal identity programs through direct regulation of neuron type-specific effector genes. We will provide here an update on recent studies that solidify the terminal selector concept in worms, flies and chordates. We will also describe how the terminal selector concept has been expanded by recent work in C. elegans to explain neuronal subtype diversification and plasticity of neuronal identity.
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Curr Opin Neurobiol,
2017]
Glia adopt remarkable shapes that are tightly coordinated with the morphologies of their neuronal partners. To achieve these precise shapes, glia and neurons exhibit coordinated morphological changes on the time scale of minutes and on size scales ranging from nanometers to hundreds of microns. Here, we review recent studies that reveal the highly dynamic, localized morphological changes of mammalian neuron-glia contacts. We then explore the power of Drosophila and C. elegans models to study coordinated changes at defined neuron-glia contacts, highlighting the use of innovative genetic and imaging tools to uncover the molecular mechanisms responsible for coordinated morphogenesis of neurons and glia.
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Nat Rev Neurosci,
2021]
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 generegulatory 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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Trends Neurosci,
2010]
Neuron-type specific gene batteries define the morphological and functional diversity of cell types in the nervous system. Here, we discuss the composition of neuron-type specific gene batteries and illustrate gene regulatory strategies which determine the unique gene expression profiles and molecular composition of individual neuronal cell types from C. elegans to higher vertebrates. Based on principles learned from prokaryotic gene regulation, we argue that neuronal terminal gene batteries are functionally grouped into parallel-acting 'regulons'. The theoretical concepts discussed here provide testable hypotheses for future experimental analysis of the exact gene-regulatory mechanisms employed in the generation of neuronal diversity and identity.