Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4821-4833 ◽  
Author(s):  
N.L. Brown ◽  
S. Kanekar ◽  
M.L. Vetter ◽  
P.K. Tucker ◽  
D.L. Gemza ◽  
...  

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.

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.


Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 737-749 ◽  
Author(s):  
S.M. Parkhurst ◽  
H.D. Lipshitz ◽  
D. Ish-Horowicz

Sex determination in Drosophila depends on X-linked ‘numerator’ genes activating early Sex-lethal (Sxl) transcription in females. One numerator gene, sisterless-b (sis-b), corresponds to the achaete-scute (AS-C) T4 basic-helix-loop-helix (bHLH) gene. Two other closely related AS-C bHLH genes, T3 and T5, appear not to function as numerator elements. We analyzed endogenous AS-C expression and show that T4 is the major AS-C numerator gene because it is expressed earlier and more strongly than are T3 and T5. Only T4 expression is detectable during the early syncytial stages when Sxl state is being determined. Nevertheless, the effects of ectopic AS-C gene expression show that T3 and T5 proteins display weak but significant feminizing activities, enhancing male-lethality, and rescuing the female-lethality of sis mutations. Detailed examination of Sxl expression in rescued embryos suggests that female cells may be viable in the absence of detectable Sxl protein expression.


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.


1994 ◽  
Vol 14 (6) ◽  
pp. 4145-4154
Author(s):  
P Armand ◽  
A C Knapp ◽  
A J Hirsch ◽  
E F Wieschaus ◽  
M D Cole

We have found that a novel basic helix-loop-helix (bHLH) protein is expressed almost exclusively in the epidermal attachments sites for the somatic muscles of Drosophila melanogaster. A Drosophila cDNA library was screened with radioactively labeled E12 protein, which can dimerize with many HLH proteins. One clone that emerged from this screen encoded a previously unknown protein of 360 amino acids, named delilah, that contains both basic and HLH domains, similar to a group of cellular transcription factors implicated in cell type determination. Delilah protein formed heterodimers with E12 that bind to the muscle creatine kinase promoter. In situ hybridization with the delilah cDNA localized the expression of the gene to a subset of cells in the epidermis which form a distinct pattern involving both the segmental boundaries and intrasegmental clusters. This pattern was coincident with the known sites of attachment of the somatic muscles to tendon cells in the epidermis. delilah expression persists in snail mutant embryos which lack mesoderm, indicating that expression of the gene was not induced by attachment of the underlying muscles. The similarity of this gene to other bHLH genes suggests that it plays an important role in the differentiation of epidermal cells into muscle attachment sites.


Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1169-1178 ◽  
Author(s):  
W.C. Jen ◽  
D. Wettstein ◽  
D. Turner ◽  
A. Chitnis ◽  
C. Kintner

Segmentation of the vertebrate embryo begins when the paraxial mesoderm is subdivided into somites, through a process that remains poorly understood. To study this process, we have characterized X-Delta-2, which encodes the second Xenopus homolog of Drosophila Delta. Strikingly, X-Delta-2 is expressed within the presomitic mesoderm in a set of stripes that corresponds to prospective somitic boundaries, suggesting that Notch signaling within this region establishes a segmental prepattern prior to somitogenesis. To test this idea, we introduced antimorphic forms of X-Delta-2 and Xenopus Suppressor of Hairless (X-Su(H)) into embryos, and assayed the effects of these antimorphs on somite formation. In embryos expressing these antimorphs, the paraxial mesoderm differentiated normally into somitic tissue, but failed to segment properly. Both antimorphs also disrupted the segmental expression of X-Delta-2 and Hairy2A, a basic helix-loop-helix (bHLH) gene, within the presomitic mesoderm. These observations suggest that X-Delta-2, via X-Notch-1, plays a role in segmentation, by mediating cell-cell interactions that underlie the formation of a segmental prepattern prior to somitogenesis.


Author(s):  
Jingjing Geng ◽  
Tonglu Wei ◽  
Yue Wang ◽  
Xiaosan Huang ◽  
Ji-Hong Liu

Abstract The basic helix-loop-helix (bHLH) family of transcription factors (TFs) plays a crucial role in regulating plant response to abiotic stress by targeting a large spectrum of stress-responsive genes. However, the physiological mechanisms underlying the TF-mediated stress response are still poorly understood for most of the bHLH genes. In this study, transgenic pummelo (Citrus grandis) plants overexpressing PtrbHLH, a TF previously identified from Poncirus trifoliata, were generated via Agrobacterium-mediated transformation. In comparison with the wild-type plants, the transgenic lines exhibited significantly lower electrolyte leakage and malondialdehyde content after cold treatment, thereby resulting in a more tolerant phenotype. Meanwhile, the transgenic lines accumulated dramatically lower reactive oxygen species (ROS) levels, consistent with elevated activity and expression levels of antioxidant enzymes (genes), including catalase (CAT), peroxidase and superoxide dismutase. In addition, PtrbHLH was shown to specifically bind to and activate the promoter of PtrCAT gene. Taken together, these results demonstrated that overexpression of PtrbHLH leads to enhanced cold tolerance in transgenic pummelo, which may be due, at least partly, to modulation of ROS levels by regulating the CAT gene.


Genome ◽  
2014 ◽  
Vol 57 (10) ◽  
pp. 525-536 ◽  
Author(s):  
Xiao-Ting Liu ◽  
Yong Wang ◽  
Xu-Hua Wang ◽  
Xia-Fang Tao ◽  
Qin Yao ◽  
...  

Basic helix-loop-helix (bHLH) proteins are highly conserved DNA-binding transcription factors of a large superfamily. Animal bHLH proteins play important regulatory roles in various developmental processes such as neurogenesis, myogenesis, heart development, and hematopoiesis. The jewel wasp (Nasonia vitripennis) is a good model organism of hymenoptera insects for studies of developmental and evolutionary genetics. In this study, we identified 48 bHLH genes in the genome of N. vitripennis. According to phylogenetic analysis, based on N. vitripennis bHLH (NvbHLH) motif sequences and structural domain distribution in their full-length protein sequences, the identified NvbHLH genes were classified into 36 bHLH families with 19, 12, 9, 1, 6, and 1 member(s) in groups A, B, C, D, E, and F, respectively. Our classification to the identified NvbHLH family members confirms GenBank annotations for 21 of the 48 NvbHLH proteins and provides useful information for further characterization and annotation of the remaining 27 NvbHLH proteins. Compared to other insect species, N. vitripennis has the lowest number of bHLH family members. No NvbHLH members have been found in the families Net, MyoRa, and PTFa, while all other insect species have at least one member in each of the families. These data constitute a solid basis for further investigations into the functions of bHLH proteins in developmental regulation of N. vitripennis.


1994 ◽  
Vol 14 (8) ◽  
pp. 5259-5267
Author(s):  
S S Rao ◽  
C Chu ◽  
D S Kohtz

Activation of muscle gene transcription in differentiating skeletal myoblasts requires their withdrawal from the cell cycle. The effects of ectopic cyclin expression on activation of muscle gene transcription by myogenic basic helix-loop-helix (bHLH) regulators were investigated. Ectopic expression of cyclin D1, but not cyclins A, B1, B2, C, D3, and E, inhibited transcriptional activation of muscle gene reporter constructs by myogenic bHLH regulators in a dose-dependent manner. Ectopic expression of cyclin D1 inhibited the activity of a myogenic bHLH regulator mutant lacking the basic region protein kinase C site, indicating that phosphorylation of this site is not relevant to the mechanism of inhibition. Analysis of cyclin D1 mutants revealed that the C-terminal acidic region was required for inhibition of myogenic bHLH regulator activity, whereas an intact N-terminal pRb binding motif was not essential. Together, these results implicate expression of cyclin D1 as a central determinant of a putatively novel mechanism that links positive control of cell cycle progression to negative regulation of genes expressed in differentiated myocytes.


Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2933-2943 ◽  
Author(s):  
S. Bae ◽  
Y. Bessho ◽  
M. Hojo ◽  
R. Kageyama

We have isolated the basic helix-loop-helix (bHLH) gene Hes6, a novel member of the family of mammalian homologues of Drosophila hairy and Enhancer of split. Hes6 is expressed by both undifferentiated and differentiated cells, unlike Hes1, which is expressed only by the former cells. Hes6 alone does not bind to the DNA but suppresses Hes1 from repressing transcription. In addition, Hes6 suppresses Hes1 from inhibiting Mash1-E47 heterodimer and thereby enables Mash1 and E47 to upregulate transcription in the presence of Hes1. Furthermore, misexpression of Hes6 with retrovirus in the developing retina promotes rod photoreceptor differentiation, like Mash1, in sharp contrast to Hes1, which inhibits cell differentiation. These results suggest that Hes6 is an inhibitor of Hes1, supports Mash1 activity and promotes cell differentiation. Mutation analysis revealed that Hes1- and Hes6-specific functions are, at least in part, interchangeable by alteration of the loop region, suggesting that the loop is not simply a nonfunctional spacer but plays an important role in the specific functions.


Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3021-3030 ◽  
Author(s):  
L. Cai ◽  
E.M. Morrow ◽  
C.L. Cepko

To investigate the role(s) of basic helix-loop-helix genes (bHLH) genes in the developing murine cerebral cortex, Mash1, Math2, Math3, Neurogenin1 (Ngn1), Ngn2, NeuroD, NeuroD2 and Id1 were transduced in vivo into the embryonic and postnatal cerebral cortex using retrovirus vectors. The morphology and location of infected cells were analyzed at postnatal stages. The data indicate that a subset of bHLH genes are capable of regulating the choice of neuronal versus glial fate and that, when misexpressed, they can be deleterious to the survival of differentiating neurons, but not glia.


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