Abstract Background The sequestration of Muscleblind splicing regulators results in myotonic dystrophy. Previous work on Muscleblind has largely focused on its roles in muscle development and maintenance due to the skeletal and cardiac muscle degeneration phenotype observed in individuals with the disorder. However, a number of reported nervous system defects suggest that Muscleblind proteins function in other tissues as well. Results We have identified a mutation in the Caenorhabditis elegans homolog of Muscleblind, mbl-1, that is required for proper formation of neuromuscular junction (NMJ) synapses. mbl-1 mutants exhibit selective loss of the most distal NMJ synapses in a C. elegans motorneuron, DA9, visualized using the vesicle-associated protein RAB-3, as well as the active zone proteins SYD-2/liprin-α and UNC-10/Rim. The proximal NMJs appear to have normal pre- and postsynaptic specializations. Surprisingly, expressing a mbl-1 transgene in the presynaptic neuron is sufficient to rescue the synaptic defect, while muscle expression has no effect. Consistent with this result, mbl-1 is also expressed in neurons. Conclusions Based on these results, we conclude that in addition to its functions in muscle, the Muscleblind splice regulators also function in neurons to regulate synapse formation.

Genetic and fine structure analysis of unc-26(IV) and adjacent regions in Caenorhabditis elegans. The genetic organization of unc-26(IV) and adjacent regions was studied in Caenorhabditis elegans. We constructed a fine structure genetic map of unc-26(IV), a gene that affects locomotion and pharyngeal muscle movement but not muscle structure. Eleven alleles were positioned relative to each other recombinationally and were classified according to phenotypic severity. The unc-26 gene spans at least 0.026 map units, which is exceptionally large for a C. elegans gene. All but one allele, e205, are amorphic alleles. Interestingly, e205 is hypomorphic but also suppressible by the amber suppressor sup-7. Nineteen lethal mutations in the unc-26 region were isolated and characterized. The unc-26 region is subdivided into four zones by five deficiency breakpoints. These mutations fall into 15 complementation groups. The stages of development affected by these mutations were determined. Published in Molecular & general genetics : MGG (1990)

erbilt.edu Issue date 2021 Aug 5. PMC Copyright notice PMCID: PMC8710130  NIHMSID: NIHMS1716840  PMID: 34237253 The publisher's version of this article is available at Cell Summary We have produced expression profiles of all 302 neurons of the C. elegans nervous system that match the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses distinct codes of ~23 neuropeptide genes and ~36 neuropeptide receptors, delineating a complex and expansive “wireless” signaling network. To demonstrate the utility of this comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression and (2) reveal adhesion proteins with potential roles in process placement and synaptic specificity. Our expression data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system. In Brief A gene expression map captures all 302 neurons in mature C. elegans deciphering the molecular basis for cell heterogeneity, connectivity and function. Graphical Abstract INTRODUCTION Neurons share many common functions, yet there are a remarkable variety of different neuronal types, each with distinct features and functions. As genetic programs likely specify these differences, a comprehensive molecular model of the brain requires a gene expression map at single-cell resolution. Although profiling methods have catalogued diverse neuron types in a variety of organisms ( Adorjan et al., 2019 ; Poulin et al., 2016 ; Tasic et al., 2016 ; Zeisel et al., 2015 ; Zhu et al., 2018 ), incomplete knowledge of the anatomy and wiring of complex n