Dataset Information

Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans.

ABSTRACT: Although Hox genes specify the differentiation of neuronal subtypes along the anterior-posterior axis, their mode of action is not entirely understood. Using two subtypes of the touch receptor neurons (TRNs) in C. elegans, we found that a "posterior induction" mechanism underlies the Hox control of terminal neuronal differentiation. The anterior subtype maintains a default TRN state, whereas the posterior subtype undergoes further morphological and transcriptional specification induced by the posterior Hox proteins, mainly EGL-5/Abd-B. Misexpression of the posterior Hox proteins transformed the anterior TRN subtype toward a posterior identity both morphologically and genetically. The specification of the posterior subtype requires EGL-5-induced repression of TALE cofactors, which antagonize EGL-5 functions, and the activation of rfip-1, a component of recycling endosomes, which mediates Hox activities by promoting subtype-specific neurite outgrowth. Finally, EGL-5 is required for subtype-specific circuit formation by acting in both the sensory neuron and downstream interneuron to promote functional connectivity.

SUBMITTER: Zheng C

PROVIDER: S-EPMC4635444 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans.

Zheng Chaogu C Diaz-Cuadros Margarete M Chalfie Martin M

Neuron 20151101 3

Although Hox genes specify the differentiation of neuronal subtypes along the anterior-posterior axis, their mode of action is not entirely understood. Using two subtypes of the touch receptor neurons (TRNs) in C. elegans, we found that a "posterior induction" mechanism underlies the Hox control of terminal neuronal differentiation. The anterior subtype maintains a default TRN state, whereas the posterior subtype undergoes further morphological and transcriptional specification induced by the po ...[more]

PMID: 26539892

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Project description:BackgroundHox genes are key elements in patterning animal development. They are renowned for their, often, clustered organisation in the genome, with supposed mechanistic links between the organisation of the genes and their expression. The widespread distribution and comparable functions of Hox genes across the animals has led to them being a major study system for comparing the molecular bases for construction and divergence of animal morphologies. Echinoderms (including sea urchins, sea stars, sea cucumbers, feather stars and brittle stars) possess one of the most unusual body plans in the animal kingdom with pronounced pentameral symmetry in the adults. Consequently, much interest has focused on their development, evolution and the role of the Hox genes in these processes. In this context, the organisation of echinoderm Hox gene clusters is distinctive. Within the classificatory system of Duboule, echinoderms constitute one of the clearest examples of Disorganized (D) clusters (i.e. intact clusters but with a gene order or orientation rearranged relative to the ancestral state).ResultsHere we describe two Hox genes (Hox11/13d and e) that have been overlooked in most previous work and have not been considered in reconstructions of echinoderm Hox complements and cluster organisation. The two genes are related to Posterior Hox genes and are present in all classes of echinoderm. Importantly, they do not reside in the Hox cluster of any species for which genomic linkage data is available.ConclusionIncorporating the two neglected Posterior Hox genes into assessments of echinoderm Hox gene complements and organisation shows that these animals in fact have Split (S) Hox clusters rather than simply Disorganized (D) clusters within the Duboule classification scheme. This then has implications for how these genes are likely regulated, with them no longer covered by any potential long-range Hox cluster-wide, or multigenic sub-cluster, regulatory mechanisms.

Project description:Neurogenesis involves the precisely-coordinated action of genetic programs controlling large-scale neuronal fate specification down to terminal events of neuronal differentiation. The Q neuroblasts in C. elegans, QL on the left and QR on the right, divide, differentiate, and migrate in a similar pattern to produce three neurons each. However, QL on the left migrates posteriorly, and QR on the right migrates anteriorly. The MAB-5/Hox transcription factor is necessary and sufficient for posterior Q lineage migration, and is normally expressed only in the QL lineage. To define genes controlled by MAB-5 in the Q cells, fluorescence-activated cell sorting was utilized to isolate populations of Q cells at a time in early L1 larvae when MAB-5 first becomes active. Sorted Q cells from wild-type, mab-5 loss-of-function (lof), and mab-5 gain-of-function (gof) mutants were subject to RNA-seq and differential expression analysis. Genes enriched in Q cells included those involved in cell division, DNA replication, and DNA repair, consist with the neuroblast stem cell identity of the Q cells at this stage. Genes affected by mab-5 included those involved in neurogenesis, neural development, and interaction with the extracellular matrix. cwn-1, which encodes a Wnt signaling molecule, showed a paired response to mab-5 in the Q cells: cwn-1 expression was reduced in mab-5(lof) and increased in mab-5(gof), suggesting that MAB-5 is required for cwn-1 expression in Q cells. MAB-5 is required to prevent anterior migration of the Q lineage while it transcriptionally reprograms the Q lineage for posterior migration. Functional genetic analysis revealed that CWN-1 is required downstream of MAB-5 to inhibit anterior migration of the QL lineage, likely in parallel to EGL-20/Wnt in a non-canonical Wnt pathway. In sum, work here describes a Q cell transcriptome, and a set of genes regulated by MAB-5 in the QL lineage. One of these genes, cwn-1, acts downstream of mab-5 in QL migration, indicating that this gene set includes other genes utilized by MAB-5 to facilitate posterior neuroblast migration.

Dataset Information

Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans.

Publications

Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans.

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