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1. An atlas of neural crest lineages along the posterior developing zebrafish at single-cell resolution

   https://doi.org/10.7554/eLife.60005  

   Howard, Aubrey GA; Baker, Phillip A; Ibarra-García-Padilla, Rodrigo; Moore, Joshua A; Rivas, Lucia J; Tallman, James J; Singleton, Eileen W; Westheimer, Jessa L; Corteguera, Julia A; Uribe, Rosa A (February 2021, eLife)

   Neural crest cells (NCCs) are vertebrate stem cells that give rise to various cell types throughout the developing body in early life. Here, we utilized single-cell transcriptomic analyses to delineate NCC-derivatives along the posterior developing vertebrate, zebrafish, during the late embryonic to early larval stage, a period when NCCs are actively differentiating into distinct cellular lineages. We identified several major NCC/NCC-derived cell-types including mesenchyme, neural crest, neural, neuronal, glial, and pigment, from which we resolved over three dozen cellular subtypes. We dissected gene expression signatures of pigment progenitors delineating into chromatophore lineages, mesenchyme cells, and enteric NCCs transforming into enteric neurons. Global analysis of NCC derivatives revealed they were demarcated by combinatorial hox gene codes, with distinct profiles within neuronal cells. From these analyses, we present a comprehensive cell-type atlas that can be utilized as a valuable resource for further mechanistic and evolutionary investigations of NCC differentiation. 

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2. microRNA‐124 regulates Notch and NeuroD1 to mediate transition states of neuronal development

   https://doi.org/10.1002/dneu.22902  

   Konrad, Kalin D.; Song, Jia L. (November 2022, Developmental Neurobiology)

   Abstract MicroRNAs regulate gene expression by destabilizing target mRNA and/or inhibiting translation in animal cells. The ability to mechanistically dissect miR‐124′s function during specification, differentiation, and maturation of neurons during development within a single system has not been accomplished. Using the sea urchin embryo, we take advantage of the manipulability of the embryo and its well‐documented gene regulatory networks (GRNs). We incorporatedNeuroD1as part of the sea urchin neuronal GRN and determined that miR‐124 inhibition resulted in aberrant gut contractions, swimming velocity, and neuronal development. Inhibition of miR‐124 resulted in an increased number of cells expressing transcription factors (TFs) associated with progenitor neurons and a concurrent decrease of mature and functional neurons. Results revealed that in the early blastula/gastrula stages, miR‐124 regulates undefined factors during neuronal specification and differentiation. In the late gastrula/larval stages, miR‐124 regulatesNotchandNeuroD1during the transition between neuronal differentiation and maturation. Overall, we have improved the neuronal GRN and identified miR‐124 to play a prolific role in regulating various transitions of neuronal development. 

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3. Ebf Activates Expression of a Cholinergic Locus in a Multipolar Motor Ganglion Interneuron Subtype in Ciona

   https://doi.org/10.3389/fnins.2021.784649  

   Popsuj, Sydney; Stolfi, Alberto (December 2021, Frontiers in Neuroscience)

   Conserved transcription factors termed “terminal selectors” regulate neuronal sub-type specification and differentiation through combinatorial transcriptional regulation of terminal differentiation genes. The unique combinations of terminal differentiation gene products in turn contribute to the functional identities of each neuron. One well-characterized terminal selector is COE (Collier/Olf/Ebf), which has been shown to activate cholinergic gene batteries in C. elegans motor neurons. However, its functions in other metazoans, particularly chordates, is less clear. Here we show that the sole COE ortholog in the non-vertebrate chordate Ciona robusta , Ebf, controls the expression of the cholinergic locus VAChT/ChAT in a single dorsal interneuron of the larval Motor Ganglion, which is presumed to be homologous to the vertebrate spinal cord. We propose that, while the function of Ebf as a regulator of cholinergic neuron identity conserved across bilaterians, its exact role may have diverged in different cholinergic neuron subtypes (e.g., interneurons vs. motor neurons) in chordate-specific motor circuits. 

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4. Drosophila female reproductive tract gene expression reveals coordinated mating responses and rapidly evolving tissue-specific genes

   https://doi.org/10.1093/g3journal/jkab020  

   McDonough-Goldstein, Caitlin E; Borziak, Kirill; Pitnick, Scott; Dorus, Steve (March 2021, G3 Genes|Genomes|Genetics)

   Civetta, A (Ed.)

   Abstract Sexual reproduction in internally fertilizing species requires complex coordination between female and male reproductive systems and among the diverse tissues of the female reproductive tract (FRT). Here, we report a comprehensive, tissue-specific investigation of Drosophila melanogaster FRT gene expression before and after mating. We identified expression profiles that distinguished each tissue, including major differences between tissues with glandular or primarily nonglandular epithelium. All tissues were enriched for distinct sets of genes possessing secretion signals that exhibited accelerated evolution, as might be expected for genes participating in molecular interactions between the sexes within the FRT extracellular environment. Despite robust transcriptional differences between tissues, postmating responses were dominated by coordinated transient changes indicative of an integrated systems-level functional response. This comprehensive characterization of gene expression throughout the FRT identifies putative female contributions to postcopulatory events critical to reproduction and potentially reproductive isolation, as well as the putative targets of sexual selection and conflict. 

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5. Hox proteins interact to pattern neuronal subtypes in Caenorhabditis elegans males

   https://doi.org/10.1093/genetics/iyac010  

   Kalis, Andrea K; Sterrett, Maria C; Armstrong, Cecily; Ballmer, Amarantha; Burkstrand, Kylie; Chilson, Elizabeth; Emlen, Estee; Ferrer, Emma; Loeb, Seanna; Olin, Taylor; et al (February 2022, Genetics)

   Hobert, O (Ed.)

   Abstract Hox transcription factors are conserved regulators of neuronal subtype specification on the anteroposterior axis in animals, with disruption of Hox gene expression leading to homeotic transformations of neuronal identities. We have taken advantage of an unusual mutation in the Caenorhabditis elegans Hox gene lin-39, lin-39(ccc16), which transforms neuronal fates in the C. elegans male ventral nerve cord in a manner that depends on a second Hox gene, mab-5. We have performed a genetic analysis centered around this homeotic allele of lin-39 in conjunction with reporters for neuronal target genes and protein interaction assays to explore how LIN-39 and MAB-5 exert both flexibility and specificity in target regulation. We identify cis-regulatory modules in neuronal reporters that are both region-specific and Hox-responsive. Using these reporters of neuronal subtype, we also find that the lin-39(ccc16) mutation disrupts neuronal fates specifically in the region where lin-39 and mab-5 are coexpressed, and that the protein encoded by lin-39(ccc16) is active only in the absence of mab-5. Moreover, the fates of neurons typical to the region of lin-39-mab-5 coexpression depend on both Hox genes. Our genetic analysis, along with evidence from Bimolecular Fluorescence Complementation protein interaction assays, supports a model in which LIN-39 and MAB-5 act at an array of cis-regulatory modules to cooperatively activate and to individually activate or repress neuronal gene expression, resulting in regionally specific neuronal fates. 

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