pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo

Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. We found that the expression of five anterior-specific genes in Caenorhabditis elegans embryos depends on the Wnt pathway effectors pop-1/TCF and sys-1/β-catenin. We focused further on one of these anterior genes, ref-2/ZIC, a conserved transcription factor expressed in multiple anterior lineages. Live imaging of ref-2 mutant embryos identified defects in cell division timing and position in anterior lineages. Cis-regulatory dissection identified three ref-2 transcriptional enhancers, one of which is necessary and sufficient for anterior-specific expression. This enhancer is activated by the T-box transcription factors TBX-37 and TBX-38, and surprisingly, concatemerized TBX-37/38 binding sites are sufficient to drive anterior-biased expression alone, despite the broad expression of TBX-37 and TBX-38. Taken together, our results highlight the diverse mechanisms used to regulate anterior expression patterns in the embryo.

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The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos

Development ◽

10.1242/dev.124.19.3815 ◽

1997 ◽

Vol 124 (19) ◽

pp. 3815-3826 ◽

Cited By ~ 4

Author(s):

B. Bowerman ◽

M.K. Ingram ◽

C.P. Hunter

Keyword(s):

Cell Fate ◽

Expression Patterns ◽

Control Cell ◽

Gene Products ◽

Cell Fate Specification ◽

Loss Of Function ◽

C Elegans ◽

Embryonic Polarity ◽

Early Embryos ◽

Anterior Posterior

After fertilization in C. elegans, activities encoded by the maternally expressed par genes appear to establish cellular and embryonic polarity. Loss-of-function mutations in the par genes disrupt anterior-posterior (a-p) asymmetries in early embryos and result in highly abnormal patterns of cell fate. Little is known about how the early asymmetry defects are related to the cell fate patterning defects in par mutant embryos, or about how the par gene products affect the localization and activities of developmental regulators known to specify the cell fate patterns made by individual blastomeres. Examples of such regulators of blastomere identity include the maternal proteins MEX-3 and GLP-1, expressed at high levels anteriorly, and SKN-1 and PAL-1, expressed at high levels posteriorly in early embryos. To better define par gene functions, we examined the expression patterns of MEX-3, PAL-1 and SKN-1, and we analyzed mex-3, pal-1, skn-1 and glp-1 activities in par mutant embryos. We have found that mutational inactivation of each par gene results in a unique phenotype, but in no case do we observe a complete loss of a-p asymmetry. We conclude that no one par gene is required for all a-p asymmetry and we suggest that, in some cases, the par genes act independently of each other to control cell fate patterning and polarity. Finally, we discuss the implications of our findings for understanding how the initial establishment of polarity in the zygote by the par gene products leads to the proper localization of more specifically acting regulators of blastomere identity.

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Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos

The Journal of Cell Biology ◽

10.1083/jcb.201408064 ◽

2015 ◽

Vol 208 (6) ◽

pp. 661-669 ◽

Cited By ~ 24

Author(s):

Nicolas Tavernier ◽

Anna Noatynska ◽

Costanza Panbianco ◽

Lisa Martino ◽

Lucie Van Hove ◽

...

Keyword(s):

Feedback Loop ◽

Molecular Mechanisms ◽

Aurora A ◽

Positive Feedback Loop ◽

Mitotic Entry ◽

Animal Development ◽

C Elegans ◽

Mitotic Kinase ◽

Cell Division Timing

The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho–SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing.

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FMRFamide-like peptides in root knot nematodes and their potential role in nematode physiology

Journal of Helminthology ◽

10.1017/s0022149x09990630 ◽

2009 ◽

Vol 84 (3) ◽

pp. 253-265 ◽

Cited By ~ 15

Author(s):

M.J.G. Johnston ◽

P. McVeigh ◽

S. McMaster ◽

C.C. Fleming ◽

A.G. Maule

Keyword(s):

Expression Patterns ◽

Single Copy ◽

The Novel ◽

Specific Expression ◽

Root Knot Nematodes ◽

C Elegans ◽

Free Living Nematode ◽

Rapid Amplification ◽

Race Pcr ◽

High Degree

AbstractFMRFamide-like peptides (FLPs) are a diverse group of neuropeptides that are expressed abundantly in nematodes. They exert potent physiological effects on locomotory, feeding and reproductive musculature and also act as neuromodulators. However, little is known about the specific expression patterns and functions of individual peptides. The current study employed rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR) to characterizeflpgenes from infective juveniles of the root knot nematodes,Meloidogyne incognitaandMeloidogyne minor. The peptides identified from these transcripts are sequelogs of FLPs from the free-living nematode,Caenorhabditis elegans; the genes have therefore been designated asMi-flp-1,Mi-flp-7,Mi-flp-12,Mm-flp-12andMi-flp-14.Mi-flp-1encodes five FLPs with the common C-terminal moiety, NFLRFamide.Mi-flp-7encodes two copies of APLDRSALVRFamide and APLDRAAMVRFamide and one copy of APFDRSSMVRFamide.Mi-flp-12andMm-flp-12encode the novel peptide KNNKFEFIRFamide (a longer version of RNKFEFIRFamide found inC. elegans).Mi-flp-14encodes a single copy of KHEYLRFamide (commonly known as AF2 and regarded as the most abundant nematode FLP), and a single copy of the novel peptide KHEFVRFamide. These FLPs share a high degree of conservation betweenMeloidogynespecies and nematodes from other clades, including those of humans and animals, perhaps suggesting a common neurophysiological role which may be exploited by novel drugs. FLP immunoreactivity was observed for the first time inMeloidogyne, in the circumpharyngeal nerve ring, pharyngeal nerves and ventral nerve cord. Additionally,in situhybridization revealedMi-flp-12expression in an RIR-like neuron andMi-flp-14expression in SMB-like neurons‡, respectively. These localizations imply physiological roles for FLP-12 and FLP-14 peptides, including locomotion and sensory perception.

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TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00193.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. L177-L191 ◽

Cited By ~ 18

Author(s):

Masafumi Horie ◽

Naoya Miyashita ◽

Yu Mikami ◽

Satoshi Noguchi ◽

Yasuhiro Yamauchi ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Transcription Factors ◽

Expression Patterns ◽

Differential Expression Analysis ◽

Lung Fibroblasts ◽

Specific Expression ◽

T Box ◽

Distinct Gene ◽

Super Enhancer

Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin and the underlying gene regulatory networks. Promoter-level differential expression analysis by cap analysis of gene expression (CAGE) sequencing revealed distinct gene expression patterns of fibroblasts derived from different anatomical sites and identified 88 coding genes with higher expression in lung fibroblasts relative to other fibroblasts. Multiple key transcription factors important for lung mesenchyme development, including the T-box transcription factors TBX2, TBX4, and TBX5 were enriched in this lung-specific signature and were associated with super-enhancers. TBX4 showed highly specific expression in lung fibroblasts and was required for cell proliferation and collagen gel contraction capacity. Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. Of pathological importance, lung fibroblast-specific genes were globally downregulated in lung cancer-associated fibroblasts (CAFs). Notably, TBX2, TBX4, and TBX5 were downregulated and hypermethylated in lung CAFs, suggesting an association between epigenetic silencing of these factors and phenotypic alteration of lung fibroblasts in cancer. Our study highlights the importance of T-box transcription factors, especially TBX4, and super-enhancers in the roles of lung fibroblasts in pulmonary physiology and pathogenesis.

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Expression of the homeotic gene mab-5 during Caenorhabditis elegans embryogenesis

Development ◽

10.1242/dev.116.2.481 ◽

1992 ◽

Vol 116 (2) ◽

pp. 481-490 ◽

Cited By ~ 11

Author(s):

D.W. Cowing ◽

C. Kenyon

Keyword(s):

Early Stage ◽

Postembryonic Development ◽

Early Embryogenesis ◽

Lacz Fusion ◽

Homeotic Genes ◽

Specific Expression ◽

C Elegans ◽

Developmental Factors ◽

Cell Embryo ◽

Anterior Posterior

mab-5 is a member of a complex of homeobox-containing genes evolutionarily related to the Antennapedia and bithorax complexes of Drosophila melanogaster. Like the homeotic genes in Drosophila, mab-5 is required in a particular region along the anterior-posterior body axis, and acts during postembryonic development to give cells in this region their characteristic identities. We have used a mab-5-lacZ fusion integrated into the C. elegans genome to study the posterior-specific expression of mab-5 during embryogenesis. The mab-5-lacZ fusion was expressed in the posterior of the embryo by 180 minutes after the first cleavage, indicating that the mechanisms responsible for the position-specific expression of mab-5-lacZ act at a relatively early stage of embryogenesis. In embryos homozygous for mutations in the par genes, which disrupt segregation of factors during early cleavages, expression of mab-5-lacZ was no longer localized to the posterior. This suggests that posterior-specific expression of mab-5 depends on the appropriate segregation of developmental factors during early embryogenesis. After extrusion of any blastomere of the four-cell embryo, descendants of the remaining three cells could still express the mab-5-lacZ fusion. In these partial embryos, however, the fusion was often expressed in cells scattered throughout the embryo, suggesting that cell-cell interactions and/or proper positioning of early blastomeres are required for mab-5 expression to be localized to the posterior.

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