scholarly journals Etv transcription factors functionally diverge from their upstream FGF signaling in lens development

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ankur Garg ◽  
Abdul Hannan ◽  
Qian Wang ◽  
Neoklis Makrides ◽  
Jian Zhong ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Functional Divergence ◽  
Transitional Zone ◽  
Lens Development ◽  
Fgf Receptor ◽  
Erk Phosphorylation ◽  
Normal Lens ◽  
Transcriptional Output ◽  
Fiber Gene ◽  
Mtor Activity

The signal regulated transcription factors (SRTFs) control the ultimate transcriptional output of signaling pathways. Here, we examined a family of FGF-induced SRTFs – Etv1, Etv 4, and Etv 5 – in murine lens development. Contrary to FGF receptor mutants that displayed loss of ERK signaling and defective cell differentiation, Etv deficiency augmented ERK phosphorylation without disrupting the normal lens fiber gene expression. Instead, the transitional zone for lens differentiation was shifted anteriorly as a result of reduced Jag1-Notch signaling. We also showed that Etv proteins suppresses mTOR activity by promoting Tsc2 expression, which is necessary for the nuclei clearance in mature lens. These results revealed the functional divergence between Etv and FGF in lens development, demonstrating that these SRTFs can operate outside the confine of their upstream signaling.

Expression of a truncated FGF receptor results in defective lens development in transgenic mice

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 3959-3967 ◽  
Author(s):  
M.L. Robinson ◽  
L.A. MacMillan-Crow ◽  
J.A. Thompson ◽  
P.A. Overbeek
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Polymerase Chain Reaction Amplification ◽  
Dominant Negative ◽  
Lens Epithelial Cells ◽  
Type I ◽  
Lens Development ◽  
Fgf Receptor ◽  
Surface Receptors ◽  
Normal Lens

Members of the fibroblast growth factor (FGF) family are thought to initiate biological responses through the activation of cell surface receptors which must dimerize to transmit an intracellular signal. Mammalian lens epithelial cells respond to exogenous extracellular FGF, either in tissue culture or in transgenic mice, by initiating fiber cell differentiation. The role of FGF signalling in normal lens development was evaluated by lens-specific synthesis of a kinase-deficient FGF receptor type I (FGFR1) in transgenic mice. This truncated FGF receptor is thought to act as a dominant negative protein by heterodimerization with endogenous FGF receptors. The presence of transgenic mRNA in the lens was confirmed by in situ hybridization and by polymerase chain reaction amplification of reverse transcribed lens RNA (RT-PCR). The presence of transgenic protein was determined by Western blotting with antibodies to an extracellular domain of FGFR1. Three of four transgenic families expressing the truncated FGF receptor exhibited lens defects ranging from cataracts to severe microphthalmia. While the microphthalmic lenses displayed a normal pattern of differentiation-specific crystallin expression, the lens epithelial cells were reduced in number and the lens fiber cells displayed characteristics consistent with the induction of apoptosis. Our results support the view that FGF receptor signalling plays an essential role in normal lens biology.

scholarly journals Co-option of the Limb Patterning Program in Cephalopod Lens Development

2021 ◽  
Author(s):  
Stephanie Neal ◽  
Kyle J. McCulloch ◽  
Francesca Napoli ◽  
Christina M. Daly ◽  
James H. Coleman ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Functional Significance ◽  
Limb Development ◽  
Lens Development ◽  
Limb Patterning ◽  
Regulatory Relationship ◽  
Radial Patterning ◽  
Underlying Mechanisms

AbstractAcross the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Here we identify the co-option of the canonical bilaterian limb pattering program redeployed during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factorsSP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and aPrdlhomolog in the squidDoryteuthis pealeii, similar to expression required inDrosophilalimb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate this co-option. These results suggest that the limb network does not exclusively pattern appendage outgrowth but is performing a more universal developmental function: radial patterning.

scholarly journals Functional Divergence of the Arabidopsis Florigen-Interacting bZIP Transcription Factors FD and FDP

Cell Reports ◽  
2020 ◽  
Vol 31 (9) ◽  
pp. 107717 ◽  
Author(s):  
Maida Romera-Branchat ◽  
Edouard Severing ◽  
Chloé Pocard ◽  
Hyonhwa Ohr ◽  
Coral Vincent ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Functional Divergence ◽  
Bzip Transcription Factors

scholarly journals Functional Divergence of Mammalian TFAP2a and TFAP2b Transcription Factors for Bidirectional Sleep Control

Genetics ◽  
2020 ◽  
Vol 216 (3) ◽  
pp. 735-752
Author(s):  
Yang Hu ◽  
Alejandra Korovaichuk ◽  
Mariana Astiz ◽  
Henning Schroeder ◽  
Rezaul Islam ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Sleep Quality ◽  
Functional Divergence ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Dark Phase ◽  
Quiet Sleep ◽  
Sleep Behavior ◽  
Sleep Quantity ◽  
Sleep Control

Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of nonrapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in Caenorhabditiselegans and Drosophila. In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of Tfap2a and Tfap2b in sleep control in mice. Consistent with our results from C. elegans and Drosophila, the AP-2 transcription factors Tfap2a and Tfap2b also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. Tfap2a reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, Tfap2b reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in Tfap2b mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the AP-2 genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.

scholarly journals Regulation of TEAD Transcription Factors in Cancer Biology

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 600 ◽  
Author(s):  
Hyunbin Huh ◽  
Dong Kim ◽  
Han-Sol Jeong ◽  
Hyun Park
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Tumor Progression ◽  
Transforming Growth Factor Beta ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Transforming Growth Factor ◽  
Clinicopathological Parameters ◽  
Transcriptional Output

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

Promoter islandsas a platform for interaction with nucleoid proteins and transcription factors

2014 ◽  
Vol 12 (02) ◽  
pp. 1441006 ◽  
Author(s):  
Yuri A. Purtov ◽  
Olga A. Glazunova ◽  
Sergey S. Antipov ◽  
Viktoria O. Pokusaeva ◽  
Eugeny E. Fesenko ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Computer Search ◽  
Biologically Relevant ◽  
Bacterial Nucleoid ◽  
Foreign Genes ◽  
Transcriptional Output

Seventy-eight promoter islands with an extraordinarily high density of potential promoters have been recently found in the genome of Escherichia coli. It has been shown that RNA polymerase binds internal promoters of these islands and produces short oligonucleotides, while the synthesis of normal mRNAs is suppressed. This quenching may be biologically relevant, as most islands are associated with foreign genes, which expression may deplete cellular resources. However, a molecular mechanism of silencing with the participation of these promoter-rich regions remains obscure. It has been demonstrated that all islands interact with histone-like protein H-NS — a specific sentinel of foreign genes. In this study, we demonstrated the inhibitory effect of H-NS using Δhns mutant of Escherichia coli and showed that deletion of dps, encoding another protein of bacterial nucleoid, tended to decrease rather than increase the amount of island-specific transcripts. This observation precluded consideration of promoter islands as sites for targeted heterochromatization only and a computer search for the binding sites of 53 transcription factors (TFs) revealed six proteins, which may specifically regulate their transcriptional output.

scholarly journals Severe Defects in Proliferation and Differentiation of Lens Cells in Foxe3 Null Mice

2005 ◽  
Vol 25 (20) ◽  
pp. 8854-8863 ◽  
Author(s):  
Olga Medina-Martinez ◽  
Isaac Brownell ◽  
Felipe Amaya-Manzanares ◽  
Qiyong Hu ◽  
Richard R. Behringer ◽  
...  
Keyword(s):  
Lens Epithelium ◽  
Abnormal Development ◽  
Distinct Region ◽  
Lens Development ◽  
Forkhead Transcription Factor ◽  
Surface Ectoderm ◽  
Dnase Ii ◽  
Lens Cells ◽  
Acid Dnase ◽  
Normal Lens

ABSTRACT During mouse eye development, the correct formation of the lens occurs as a result of reciprocal interactions between the neuroectoderm that forms the retina and surface ectoderm that forms the lens. Although many transcription factors required for early lens development have been identified, the mechanism and genetic interactions mediated by them remain poorly understood. Foxe3 encodes a winged helix-forkhead transcription factor that is initially expressed in the developing brain and in the lens placode and later restricted exclusively to the anterior lens epithelium. Here, we show that targeted disruption of Foxe3 results in abnormal development of the eye. Cells of the anterior lens epithelium show a decreased rate of proliferation, resulting in a smaller than normal lens. The anterior lens epithelium does not properly separate from the cornea and frequently forms an unusual, multilayered tissue. Because of the abnormal differentiation, lens fiber cells do not form properly, and the morphogenesis of the lens is greatly affected. The abnormally differentiated lens cells remain irregular in shape, and the lens becomes vacuolated. The defects in lens development correlate with changes in the expression of growth and differentiation factor genes, including DNase II-like acid DNase, Prox1, p57, and PDGFα receptor. As a result of abnormal lens development, the cornea and the retina are also affected. While Foxe3 is also expressed in a distinct region of the embryonic brain, we have not observed abnormal development of the brain in Foxe3 −/− animals.

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