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

2017 ◽  
Author(s):  
E Perea-Atienza ◽  
S.G. Sprecher ◽  
P Martínez

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.

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1295-1304 ◽  
Author(s):  
Z. Kozmik ◽  
N.D. Holland ◽  
A. Kalousova ◽  
J. Paces ◽  
M. Schubert ◽  
...  

On the basis of developmental gene expression, the vertebrate central nervous system comprises: a forebrain plus anterior midbrain, a midbrain-hindbrain boundary region (MHB) having organizer properties, and a rhombospinal domain. The vertebrate MHB is characterized by position, by organizer properties and by being the early site of action of Wnt1 and engrailed genes, and of genes of the Pax2/5/8 subfamily. Wada and others (Wada, H., Saiga, H., Satoh, N. and Holland, P. W. H. (1998) Development 125, 1113–1122) suggested that ascidian tunicates have a vertebrate-like MHB on the basis of ascidian Pax258 expression there. In another invertebrate chordate, amphioxus, comparable gene expression evidence for a vertebrate-like MHB is lacking. We, therefore, isolated and characterized AmphiPax2/5/8, the sole member of this subfamily in amphioxus. AmphiPax2/5/8 is initially expressed well back in the rhombospinal domain and not where a MHB would be expected. In contrast, most of the other expression domains of AmphiPax2/5/8 correspond to expression domains of vertebrate Pax2, Pax5 and Pax8 in structures that are probably homologous - support cells of the eye, nephridium, thyroid-like structures and pharyngeal gill slits; although AmphiPax2/5/8 is not transcribed in any structures that could be interpreted as homologues of vertebrate otic placodes or otic vesicles. In sum, the developmental expression of AmphiPax2/5/8 indicates that the amphioxus central nervous system lacks a MHB resembling the vertebrate isthmic region. Additional gene expression data for the developing ascidian and amphioxus nervous systems would help determine whether a MHB is a basal chordate character secondarily lost in amphioxus. The alternative is that the MHB is a vertebrate innovation.


Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1262
Author(s):  
Lenny J. Negrón-Piñeiro ◽  
Yushi Wu ◽  
Anna Di Gregorio

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.


2007 ◽  
Vol 28 (5) ◽  
pp. 1456-1469 ◽  
Author(s):  
Pierre Mattar ◽  
Lisa Marie Langevin ◽  
Kathryn Markham ◽  
Natalia Klenin ◽  
Salma Shivji ◽  
...  

ABSTRACT Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only ∼60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.


1995 ◽  
Vol 15 (11) ◽  
pp. 6036-6044 ◽  
Author(s):  
A Chiaramello ◽  
K Neuman ◽  
K Palm ◽  
M Metsis ◽  
T Neuman

Sequence analysis of rat and human low-affinity nerve growth factor receptor p75LNGFR gene promoter regions revealed a single E-box cis-acting element, located upstream of the major transcription start sites. Deletion analysis of the E-box sequence demonstrated that it significantly contributes to p75LNGFR promoter activity. This E box has a dual function; it mediates either activation or repression of the p75LNGFR promoter activity, depending on the interacting transcription factors. We showed that the two isoforms of the class A basic helix-loop-helix (bHLH) transcription factor ME1 (ME1a and ME1b), the murine homolog of the human HEB transcription factor, specifically repress p75LNGFR promoter activity. This repression can be released by coexpression of the HLH Id2 transcriptional regulator. In vitro analyses demonstrated that ME1a forms a stable complex with the p75LNGFR E box and likely competes with activating E-box-binding proteins. By using ME1a-overexpressing PC12 cells, we showed that the endogenous p75LNGFR gene is a target of ME1a repression. Together, these data demonstrate that the p75LNGFR E box and the interacting bHLH transcription factors are involved in the regulation of p75LNGFR gene expression. These results also show that class A bHLH transcription factors can repress and Id-like negative regulators can stimulate gene expression.


2008 ◽  
Vol 414 (3) ◽  
pp. 327-341 ◽  
Author(s):  
Lezanne Ooi ◽  
Ian C. Wood

The nervous system contains a multitude of cell types which are specified during development by cascades of transcription factors acting combinatorially. Some of these transcription factors are only active during development, whereas others continue to function in the mature nervous system to maintain appropriate gene-expression patterns in differentiated cells. Underpinning the function of the nervous system is its plasticity in response to external stimuli, and many transcription factors are involved in regulating gene expression in response to neuronal activity, allowing us to learn, remember and make complex decisions. Here we review some of the recent findings that have uncovered the molecular mechanisms that underpin the control of gene regulatory networks within the nervous system. We highlight some recent insights into the gene-regulatory circuits in the development and differentiation of cells within the nervous system and discuss some of the mechanisms by which synaptic transmission influences transcription-factor activity in the mature nervous system. Mutations in genes that are important in epigenetic regulation (by influencing DNA methylation and post-translational histone modifications) have long been associated with neuronal disorders in humans such as Rett syndrome, Huntington's disease and some forms of mental retardation, and recent work has focused on unravelling their mechanisms of action. Finally, the discovery of microRNAs has produced a paradigm shift in gene expression, and we provide some examples and discuss the contribution of microRNAs to maintaining dynamic gene regulatory networks in the brain.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Karen A. Hudson ◽  
Matthew E. Hudson

The complete genome sequence of soybean allows an unprecedented opportunity for the discovery of the genes controlling important traits. In particular, the potential functions of regulatory genes are a priority for analysis. The basic helix-loop-helix (bHLH) family of transcription factors is known to be involved in controlling a wide range of systems critical for crop adaptation and quality, including photosynthesis, light signalling, pigment biosynthesis, and seed pod development. Using a hidden Markov model search algorithm, 319 genes with basic helix-loop-helix transcription factor domains were identified within the soybean genome sequence. These were classified with respect to their predicted DNA binding potential, intron/exon structure, and the phylogeny of the bHLH domain. Evidence is presented that the vast majority (281) of these 319 soybean bHLH genes are expressed at the mRNA level. Of these soybean bHLH genes, 67% were found to exist in two or more homeologous copies. This dataset provides a framework for future studies on bHLH gene function in soybean. The challenge for future research remains to define functions for the bHLH factors encoded in the soybean genome, which may allow greater flexibility for genetic selection of growth and environmental adaptation in this widely grown crop.


Reproduction ◽  
2012 ◽  
Vol 144 (5) ◽  
pp. 569-582 ◽  
Author(s):  
Lisa Shaw ◽  
Sharon F Sneddon ◽  
Daniel R Brison ◽  
Susan J Kimber

Identification and characterisation of differentially regulated genes in preimplantation human embryonic development are required to improve embryo quality and pregnancy rates in IVF. In this study, we examined expression of a number of genes known to be critical for early development and compared expression profiles in individual preimplantation human embryos to establish any differences in gene expression in fresh compared to frozen–thawed embryos used routinely in IVF. We analysed expression of 19 genes by cDNA amplification followed by quantitative real-time PCR in a panel of 44 fresh and frozen–thawed human preimplantation embryos. Fresh embryos were obtained from surplus early cleavage stage embryos and frozen–thawed embryos from cryopreserved 2PN embryos. Our aim was to determine differences in gene expression between fresh and frozen–thawed human embryos, but we also identified differences in developmental expression patterns for particular genes. We show that overall gene expression among embryos of the same stage is highly variable and our results indicate that expression levels between groups did differ and differences in expression of individual genes was detected. Our results show that gene expression from frozen–thawed embryos is more consistent when compared with fresh, suggesting that cryopreserved embryos may represent a reliable source for studying the molecular events underpinning early human embryo development.


Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3703-3713 ◽  
Author(s):  
M. Bouchard ◽  
P. Pfeffer ◽  
M. Busslinger

Pax2 and Pax5 arose by gene duplication at the onset of vertebrate evolution and have since diverged in their developmental expression patterns. They are expressed in different organs of the mouse embryo except for their coexpression at the midbrain-hindbrain boundary (MHB), which functions as an organizing center to control midbrain and cerebellum development. During MHB development, Pax2 expression is initiated prior to Pax5 transcription, and Pax2(−/−) embryos fail to generate the posterior midbrain and cerebellum, whereas Pax5(−/−) mice exhibit only minor patterning defects in the same brain regions. To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the Pax2 locus. Midbrain and cerebellum development was entirely rescued in Pax2(5ki/5ki) embryos. Pax5 could furthermore completely substitute for the Pax2 function during morphogenesis of the inner ear and genital tracts, despite the fact that the Pax5 transcript of the Pax2(5ki)allele was expressed only at a fivefold lower level than the wild-type Pax2 mRNA. As a consequence, the Pax2(5ki)allele was able to rescue most but not all Pax2 mutant defects in the developing eye and kidney, both of which are known to be highly sensitive to Pax2 protein dosage. Together these data demonstrate that the transcription factors Pax2 and Pax5 have maintained equivalent biochemical functions since their divergence early in vertebrate evolution.


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