scholarly journals Piecemeal regulation of convergent neuronal lineages by bHLH transcription factors in Caenorhabditis elegans

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Neda Masoudi ◽  
Eviatar Yemini ◽  
Ralf Schnabel ◽  
Oliver Hobert
Keyword(s):  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Contralateral Side ◽  
Mirror Image ◽  
Neuronal Markers ◽  
C Elegans ◽  
Helix Loop Helix ◽  
Distinct Lineage ◽  
Bhlh Transcription Factors ◽  
Identity Transformations

ABSTRACT Cells of the same type can be generated by distinct cellular lineages that originate in different parts of the developing embryo (‘lineage convergence’). Several Caenorhabditis elegans neuron classes composed of left/right or radially symmetric class members display such lineage convergence. We show here that the C. elegans Atonal homolog lin-32 is differentially expressed in neuronal lineages that give rise to left/right or radially symmetric class members. Loss of lin-32 results in the selective loss of the expression of pan-neuronal markers and terminal selector-type transcription factors that confer neuron class-specific features. Another basic helix-loop-helix (bHLH) gene, the Achaete-Scute homolog hlh-14, is expressed in a mirror image pattern relative to lin-32 and is required to induce neuronal identity and terminal selector expression on the contralateral side of the animal. These findings demonstrate that distinct lineage histories converge via different bHLH factors at the level of induction of terminal selector identity determinants, which thus serve as integrators of distinct lineage histories. We also describe neuron-to-neuron identity transformations in lin-32 mutants, which we propose to also be the result of misregulation of terminal selector gene expression.

scholarly journals Piecemeal regulation of convergent neuronal lineages by bHLH transcription factors in C. elegans

2021 ◽  
Author(s):  
Neda Masoudi ◽  
Ralf Schnabel ◽  
Oliver Hobert
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Lineage ◽  
Contralateral Side ◽  
Mirror Image ◽  
Lineage Tracing ◽  
Bhlh Transcription Factor ◽  
C Elegans ◽  
Distinct Lineage ◽  
Identity Transformations

Classic cell lineage studies in the nematode Caenorhabditis elegans as well as recent lineage tracing in vertebrates have shown that cells of the same type can be generated by distinct cellular lineages that originate in different parts of the developing embryo ('lineage convergence'). Several C. elegans neuron classes composed of left/right or radially symmetric class members display such lineage convergence, in that individual neurons of the same class derive from distinct, non-bilaterally symmetric lineages. We show here that the C. elegans Atonal homolog lin-32/Ato, a bHLH transcription factor, is differentially expressed in neuronal lineages that give rise to left/right or radially symmetric class members. Loss of lin-32/Ato results in the selective loss of the expression of panneuronal markers and terminal selector-type transcription factors that confer neuron class-specific features. We discovered that another bHLH transcription factor, the Achaete Scute-homolog hlh-14 is expressed in mirror image pattern to lin-32/Ato in a subset of the left/right symmetric neuron pairs and is required to induce neuronal identity and terminal selector expression on the contralateral side of the animal. These findings demonstrate that distinct lineage histories converge via distinct bHLH factors on the level of induction of terminal selector identity determinants, which thus serve as integrators of distinct lineage histories. We also describe neuron-to-neuron identity transformations in lin-32/Ato mutants, which we propose to also be the result of misregulation of terminal selector gene expression.

scholarly journals Multiple neural bHLHs ensure the precision of a neuronal specification event in C. elegans

Biology Open ◽  
2021 ◽  
Author(s):  
Konstantina Filippopoulou ◽  
Carole Couillault ◽  
Vincent Bertrand
Keyword(s):  
Transcription Factors ◽  
Quantitative Imaging ◽  
Terminal Differentiation ◽  
Cholinergic Neurons ◽  
Antagonistic Effect ◽  
Specific Class ◽  
C Elegans ◽  
Neuronal Specification ◽  
Bhlh Transcription Factors ◽  
Deleterious Genes

Neural bHLH transcription factors play a key role in the early steps of neuronal specification in many animals. We have previously observed that the Achaete-Scute HLH-3, the Olig HLH-16 and their binding partner the E protein HLH-2 activate the terminal differentiation program of a specific class of cholinergic neurons, AIY, in C. elegans. Here we identify a role for a fourth bHLH, the Neurogenin NGN-1, in this process, raising the question of why so many neural bHLHs are required for a single neuronal specification event. Using quantitative imaging we show that the combined action of different bHLHs is needed to activate the correct level of expression of the terminal selector transcription factors TTX-3 and CEH-10 that subsequently initiate and maintain the expression of a large battery of terminal differentiation genes. Surprisingly, the different bHLHs have an antagonistic effect on another target, the proapoptotic BH3-only factor EGL-1, normally not expressed in AIY and otherwise detrimental for its specification. We propose that the use of multiple neural bHLHs allows robust neuronal specification while, at the same time, preventing spurious activation of deleterious genes.

scholarly journals Atoh8 in Development and Disease

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Satya Srirama Karthik Divvela ◽  
Darius Saberi ◽  
Beate Brand-Saberi
Keyword(s):  
Transcription Factors ◽  
Embryonic Development ◽  
Subcellular Location ◽  
Transcriptional Regulators ◽  
Special Group ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Disease Initiation ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins

Atoh8 belongs to a large superfamily of transcriptional regulators called basic helix-loop-helix (bHLH) proteins. bHLH proteins have been identified in a wide range of organisms from yeast to humans. The members of this special group of transcription factors were found to be involved not only in embryonic development but also in disease initiation and its progression. Given their importance in several fundamental processes, the translation, subcellular location and turnover of bHLH proteins is tightly regulated. Alterations in the expression of bHLH proteins have been associated with multiple diseases also in context with Atoh8 which seems to unfold its functions as both transcriptional activator and repressor. Like many other bHLH transcription factors, so far, Atoh8 has also been observed to be involved in both embryonic development and carcinogenesis where it mainly acts as tumor suppressor. This review summarizes our current understanding of Atoh8 structure, function and regulation and its complex and partially controversial involvement in development and disease.

PES-1 is expressed during early embryogenesis in Caenorhabditis elegans and has homology to the fork head family of transcription factors

Development ◽  
1994 ◽  
Vol 120 (3) ◽  
pp. 505-514 ◽  
Author(s):  
I.A. Hope
Keyword(s):  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Cell Lineage ◽  
Embryonic Cell ◽  
Early Embryogenesis ◽  
C Elegans ◽  
Promoter Trapping ◽  
Fork Head ◽  
Initiation Of Transcription ◽  
Beta Galactosidase

Promoter trapping has identified a gene, pes-1, which is expressed during C. elegans embryogenesis. The beta-galactosidase expression pattern, directed by the pes-1/lacZ fusion through which this gene was cloned, has been determined precisely in terms of the embryonic cell lineage and has three components. One component is in a subset of cells of the AB founder cell lineage during early embryogenesis, suggesting pes-1 may be regulated both by cell autonomous determinants and by intercellular signals. Analysis of cDNA suggests pes-1 has two sites for initiation of transcription and the two transcripts would encode related but distinct proteins. The predicted PES-1 proteins have homology to the fork head family of transcription factors and therefore may have important regulatory roles in early embryogenesis.

scholarly journals DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 109 ◽  
Author(s):  
Aleksandra Zečić ◽  
Bart P. Braeckman
Keyword(s):  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Antioxidant Defense ◽  
Lifespan Extension ◽  
Metabolic Shift ◽  
Glyoxylate Shunt ◽  
C Elegans ◽  
Forkhead Box ◽  
Metabolic Remodeling ◽  
Transcriptional Changes

DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups.

scholarly journals Specific Protein-Protein Interaction between Basic Helix-Loop-Helix Transcription Factors and Homeoproteins of the Pitx Family

2000 ◽  
Vol 20 (13) ◽  
pp. 4826-4837 ◽  
Author(s):  
Gino Poulin ◽  
Mélanie Lebel ◽  
Michel Chamberland ◽  
Francois W. Paradis ◽  
Jacques Drouin
Keyword(s):  
Transcription Factors ◽  
Critical Role ◽  
Specific Protein ◽  
Physical Interaction ◽  
Protein Protein Interaction ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Factors ◽  
Pomc Gene ◽  
Bhlh Transcription Factors

ABSTRACT Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression of NeuroD1 in pituitary corticotroph cells and a direct physical interaction between bHLH heterodimers and Pitx1 that results in transcriptional synergism. The interaction between the bHLH and homeodomains is restricted to ubiquitous (class A) bHLH and to the Pitx subfamily. Since bHLH heterodimers interact with Pitx factors through their ubiquitous moiety, this mechanism may be implicated in other developmental processes involving bHLH factors, such as neurogenesis and myogenesis.

scholarly journals Constitutive Steroidal Glycoalkaloid Biosynthesis in Tomato is Regulated by the Clade IIIe Basic Helix-Loop-Helix Transcription Factors MYC1 and MYC2

2020 ◽  
Author(s):  
Gwen Swinnen ◽  
Margaux De Meyer ◽  
Jacob Pollier ◽  
Francisco Javier Molina-Hidalgo ◽  
Evi Ceulemans ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Constitutive Expression ◽  
Defense Compounds ◽  
Specialized Metabolites ◽  
Jasmonate Signaling ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Transcription Factors

ABSTRACTSpecialized metabolites are produced by plants to fend off biotic enemies. Across the plant kingdom, the biosynthesis of these defense compounds is promoted by jasmonate signaling in which clade IIIe basic helix-loop-helix (bHLH) transcription factors take on a central role. Tomato (Solanum lycopersicum) produces cholesterol-derived steroidal glycoalkaloids (SGAs) that act as phytoanticipins against a broad variety of herbivores and pathogens. The biosynthesis of SGAs from cholesterol occurs constitutively in tomato plants and can be further stimulated by jasmonates. Here, we demonstrate that the two tomato clade IIIe bHLH transcription factors, MYC1 and MYC2, redundantly and specifically control the constitutive biosynthesis of SGAs. Double myc1 myc2 loss-of-function tomato hairy roots displayed suppressed constitutive expression of cholesterol and SGA biosynthesis genes, and consequently severely reduced levels of the main tomato SGAs α-tomatine and dehydrotomatine. In contrast, basal expression of genes involved in canonical jasmonate signaling or in the biosynthesis of highly jasmonate-inducible phenylpropanoid-polyamine conjugates was not affected. Furthermore, CRISPR-Cas9(VQR)-mediated genome editing of a specific cis-regulatory element, targeted by MYC1/2, in the promoter of a cholesterol biosynthesis gene led to decreased constitutive expression of this gene, but did not affect its jasmonate inducibility. Our results demonstrate that clade IIIe bHLH transcriptional regulators might have evolved to regulate the biosynthesis of specific constitutively accumulating specialized metabolites independent of jasmonate signaling.One sentence summaryThe clade IIIe basic helix-loop-helix transcription factors MYC1 and MYC2 control the constitutive biosynthesis of tomato steroidal glycoalkaloids and might do so independently of jasmonate signaling.

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