Transcription Factors of the bHLH Family Delineate Vertebrate Landmarks in the Nervous System of a Simple Chordate

Tunicates are marine invertebrates whose tadpole-like larvae feature a highly simplified version of the chordate body plan. Similar to their distant vertebrate relatives, tunicate larvae develop a regionalized central nervous system and form distinct neural structures, which include a rostral sensory vesicle, a motor ganglion, and a caudal nerve cord. The sensory vesicle contains a photoreceptive complex and a statocyst, and based on the comparable expression patterns of evolutionarily conserved marker genes, it is believed to include proto-hypothalamic and proto-retinal territories. The evolutionarily conserved molecular fingerprints of these landmarks of the vertebrate brain consist of genes encoding for different transcription factors, and of the gene batteries that they control, and include several members of the bHLH family. Here we review the complement of bHLH genes present in the streamlined genome of the tunicate Ciona robusta and their current classification, and summarize recent studies on proneural bHLH transcription factors and their expression territories. We discuss the possible roles of bHLH genes in establishing the molecular compartmentalization of the enticing nervous system of this unassuming chordate.

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Characterization of the bHLH Family of Transcriptional Regulators in the ACOELS. roscoffensisand their Putative Role in Neurogenesis

10.1101/237388 ◽

2017 ◽

Author(s):

E Perea-Atienza ◽

S.G. Sprecher ◽

P Martínez

Keyword(s):

Gene Expression ◽

Nervous System ◽

Transcription Factors ◽

Expression Patterns ◽

Developmental Expression ◽

Class A ◽

Helix Loop Helix ◽

Specific Subset ◽

Bhlh Genes ◽

Eukaryotic Organisms

ABSTRACTBackgroundThe basic Helix loop helix (bHLH) family of transcription factors is one of the largest superfamilies of regulatory transcription factors and are widely used in eukaryotic organisms. They play an essential role in a range of metabolic, physiological, and developmental processes, including the development of the nervous system (NS). These transcription factors have been studied in many metazoans, especially in vertebrates but also in early branching metazoan clades such as the cnidarians and sponges. However, currently very little is known about their expression in the most basally branching bilaterian group, the xenacoelomorphs. Recently, our laboratory has characterized the full complement of bHLH in the genome of two members of the Xenacoelomorpha, the xenoturbellidXenoturbella bockiand the acoelSymsagittifera roscoffensis. Understanding the patterns of bHLH gene expression in members of this phylum (in space and time) provides critical new insights into the conserved roles of the bHLH and their putative specificities in this group. Our focus is on deciphering the specific roles that these genes have in the process of neurogenesis.ResultsHere, we analyze the developmental expression of the whole complement of bHLH genes identified in the acoelS. roscoffensis.Based on their expression patterns several members of bHLH class A appear to have specific conserved roles in neurogenesis, while other class A genes (as well as members of other classes) have likely taken on more generalized functions. All gene expression patterns are described in embryos and early juveniles.ConclusionOur results suggest that the main roles of the bHLH genes ofS. roscoffensisare evolutionarily conserved, with a specific subset dedicated to patterning the nervous system: SrAscA, SrAscB, SrHes/Hey, SrNscl, SrSrebp, SrE12/E47 and SrOlig.

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Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.91.10.4451 ◽

1994 ◽

Vol 91 (10) ◽

pp. 4451-4455 ◽

Cited By ~ 87

Author(s):

Y. Qiu ◽

A. J. Cooney ◽

S. Kuratani ◽

F. J. DeMayo ◽

S. Y. Tsai ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Transcription Factors ◽

Expression Patterns ◽

Spatiotemporal Expression ◽

Upstream Promoter ◽

Mouse Central Nervous System ◽

Chicken Ovalbumin

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Expression patterns of the genes encoding BH3 domain-only protein family in the nervous system

Neuroscience Research ◽

10.1016/s0168-0102(98)82486-3 ◽

1998 ◽

Vol 31 ◽

pp. S333

Author(s):

K. Kanazawa ◽

Y. Honma ◽

T. Mori ◽

K. Imaizumi ◽

M. Tohyama ◽

...

Keyword(s):

Nervous System ◽

Expression Patterns ◽

Protein Family ◽

Bh3 Domain ◽

Genes Encoding

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Genes and homology in nervous system evolution: Comparing gene functions, expression patterns, and cell type molecular fingerprints

Theory in Biosciences ◽

10.1016/j.thbio.2005.08.002 ◽

2005 ◽

Vol 124 (2) ◽

pp. 185-197 ◽

Cited By ~ 3

Author(s):

D ARENDT

Keyword(s):

Nervous System ◽

Expression Patterns ◽

Cell Type ◽

Molecular Fingerprints ◽

System Evolution ◽

Gene Functions ◽

Nervous System Evolution

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Specific Regulation of TCP genes by miR319

10.1101/747790 ◽

2019 ◽

Author(s):

Javier F. Palatnik ◽

Detlef Weigel

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Mirna Family ◽

Gene Families ◽

Evolutionarily Conserved ◽

Genes Encoding ◽

Specific Regulation ◽

Multicellular Organisms ◽

Sequence Similarities

AbstractMicroRNAs (miRNAs) are major regulators of gene expression in multicellular organisms. Many of the evolutionarily conserved miRNAs in plants are encoded by small gene families. The miR159/miR319 family has six members of similar sequences sharing 17 nucleotides in Arabidopsis thaliana. The members of this miRNA family regulate genes encoding TCP (TEOSINTE BRANCHED1, CYCLOIDEA and PCF1/2) and MYB transcription factors. However, despite their sequence similarities, genetic evidence indicates that miR159 and miR319 fulfil different roles in vivo. Here, we confirm previous findings showing that TCP genes are not targeted by miR159. Thus, specific small sequence differences between the miRNAs allow for the specific regulation of TCP transcription factors by miR319 miRNAs.

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Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2011491118 ◽

2021 ◽

Vol 118 (8) ◽

pp. e2011491118 ◽

Cited By ~ 1

Author(s):

Ekin Bolukbasi ◽

Nathaniel S. Woodling ◽

Dobril K. Ivanov ◽

Jennifer Adcott ◽

Andrea Foley ◽

...

Keyword(s):

Nervous System ◽

Transcription Factors ◽

Cell Types ◽

Growth Factor Signaling ◽

Cell Type ◽

Model Of Alzheimer’S Disease ◽

Distinct Cell ◽

Evolutionarily Conserved ◽

Cell Type Specific ◽

Specific Mapping

Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila. Starting from published single-cell transcriptomic data, we report that forkhead (FKH) is endogenously expressed in neurons, whereas forkhead-box-O (FOXO) is expressed in glial cells. Accordingly, we find that neuronal FKH and glial FOXO exert independent prolongevity effects. We have further explored the role of neuronal FKH in a model of Alzheimer’s disease-associated neuronal dysfunction, where we find that increased neuronal FKH preserves behavioral function and reduces ubiquitinated protein aggregation. Finally, using transcriptomic profiling, we identify Atg17, a member of the Atg1 autophagy initiation family, as one FKH-dependent target whose neuronal overexpression is sufficient to extend healthy lifespan. Taken together, our results underscore the importance of cell type-specific mapping of TF activity to preserve healthy function with age.

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Pigeon foot feathering reveals conserved limb identity networks

10.1101/602987 ◽

2019 ◽

Author(s):

Elena F. Boer ◽

Hannah F. Van Hollebeke ◽

Sungdae Park ◽

Carlos R. Infante ◽

Douglas B. Menke ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Limb Development ◽

Limb Bud ◽

Differentially Expressed ◽

Evolutionarily Conserved ◽

Genes Encoding ◽

Embryonic Limb ◽

Summary Statement ◽

Limb Identity

AbstractThe tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors,PITX1andTBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation ofPITX1andTBX5expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream ofPITX1andTBX5in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conservedPITX1- andTBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.Summary statementIn feather-footed pigeons, mutant alleles ofPITX1andTBX5drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.

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Single Nuclei Sequencing Reveals Novel Insights into the Regulation of Cellular Signatures in Children with Dilated Cardiomyopathy

Circulation ◽

10.1161/circulationaha.120.051391 ◽

2021 ◽

Author(s):

Luka Nicin ◽

Wesley T. Abplanalp ◽

Anne Schänzer ◽

Anke Sprengel ◽

David John ◽

...

Keyword(s):

Heart Failure ◽

Dilated Cardiomyopathy ◽

Cardiac Fibrosis ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Cell Types ◽

Molecular Fingerprints ◽

Age Related ◽

Genes Encoding ◽

Altered Gene

Background: Dilated cardiomyopathy (DCM) is a leading cause of death in children with heart failure. The outcome of pediatric heart failure treatment is inconsistent and large cohort studies are lacking. Progress may be achieved through personalized therapy that takes age- and disease-related pathophysiology, pathology and molecular fingerprints into account. We present snRNA-seq from pediatric DCM patients as the next step in identifying cellular signatures. Methods: We performed single nuclei RNA sequencing with heart tissues from six children with DCM with an age of 0.5, 0.75, 5, 6, 12 and 13 years. Unsupervised clustering of 18,211 nuclei led to the identification of 14 distinct clusters with 6 major cell types. Results: The number of nuclei in fibroblast clusters increased with age in DCM patients, a finding that was confirmed by histological analysis and was consistent with an age-related increase in cardiac fibrosis quantified by cardiac magnetic resonance imaging. Fibroblasts of DCM patients over 6 years of age showed a profoundly altered gene expression pattern with enrichment of genes encoding fibrillary collagens, modulation of proteoglycans, switch in thrombospondin isoforms and signatures of fibroblast activation. Additionally, a population of cardiomyocytes with a high pro-regenerative profile was identified in infant DCM patients, but was absent in > 6-year-old children. This cluster showed high expression of cell cycle activators such as cyclin D family members, increased glycolytic metabolism and antioxidative genes and alterations in ß-adrenergic signaling genes. Conclusions: Novel insights into the cellular transcriptomes of hearts from pediatric DCM patients provide remarkable age-dependent changes in the expression patterns of fibroblast and cardiomyocyte genes with less fibrotic but enriched pro-regenerative signatures in infants.

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