The transcription factors KNIRPS and KNIRPS RELATED control cell migration and branch morphogenesis during Drosophila tracheal development

Cell migration during embryonic tracheal system development in Drosophila requires DPP and EGF signaling to generate the archetypal branching pattern. We show that two genes encoding the transcription factors KNIRPS and KNIRPS RELATED possess multiple and redundant functions during tracheal development. knirps/knirps related activity is necessary to mediate DPP signaling which is required for tracheal cell migration and formation of the dorsal and ventral branches. Ectopic knirps or knirps related expression in lateral tracheal cells respecifies their anteroposterior to a dorsoventral migration behavior, similar to that observed in the case of ectopic DPP expression. In dorsal tracheal cells knirps/knirps related activity represses the transcription factor SPALT; this repression is essential for secondary and terminal branch formation. However, in cells of the dorsal trunk, spalt expression is required for normal anteroposterior cell migration and morphogenesis. spalt expression is maintained by the EGF receptor pathway and, hence, some of the opposing activities of the EGF and DPP signaling pathways are mediated by spalt and knirps/knirps related. Furthermore, we provide evidence that the border between cells acquiring dorsal branch and dorsal trunk identity is established by the direct interaction of KNIRPS with a spalt cis-regulatory element.

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ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster

Development ◽

10.1242/dev.128.15.3001 ◽

2001 ◽

Vol 128 (15) ◽

pp. 3001-3015 ◽

Cited By ~ 1

Author(s):

Pamela L. Bradley ◽

Deborah J. Andrew

Keyword(s):

Cell Migration ◽

Wnt Signaling ◽

Signaling Pathways ◽

Egf Receptor ◽

Tracheal System ◽

Directed Cell Migration ◽

Posterior Migration ◽

And Function ◽

Dorsal Epidermis ◽

Anterior Posterior

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.

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Hedgehog signaling patterns the tracheal branches

Development ◽

10.1242/dev.128.9.1599 ◽

2001 ◽

Vol 128 (9) ◽

pp. 1599-1606 ◽

Cited By ~ 1

Author(s):

L. Glazer ◽

B.Z. Shilo

Keyword(s):

Cell Migration ◽

Hedgehog Signaling ◽

Egf Receptor ◽

Cell Types ◽

Fixed Number ◽

Branching Pattern ◽

Tracheal System ◽

Tracheal Cell ◽

Distinct Cell

The elaborate branching pattern of the Drosophila tracheal system originates from ten tracheal placodes on both sides of the embryo, each consisting of about 80 cells. Simultaneous cell migration from each tracheal pit in six different directions gives rise to the stereotyped branching pattern. Each branch contains a fixed number of cells. Previous work has shown that in the dorsoventral axis, localized activation of the Dpp, Wnt and EGF receptor (DER) pathways, subdivides the tracheal pit into distinct domains. We present the role of the Hedgehog (Hh) signaling system in patterning the tracheal branches. Hh is expressed in segmental stripes abutting the anterior border of the tracheal placodes. Induction of patched expression, which results from activation by Hh, demonstrates that cells in the anterior half of the tracheal pit are activated. In hh-mutant embryos migration of all tracheal branches is absent or stalled. These defects arise from a direct effect of Hh on tracheal cells, rather than by indirect effects on patterning of the ectoderm. Tracheal cell migration could be rescued by expressing Hh only in the tracheal cells, without rescuing the ectodermal defects. Signaling by several pathways, including the Hh pathway, thus serves to subdivide the uniform population of tracheal cells into distinct cell types that will subsequently be recruited into the different branches.

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Myosin II activity is not required for Drosophila tracheal branching morphogenesis

10.1101/098814 ◽

2017 ◽

Author(s):

Amanda Ochoa-Espinosa ◽

Stefan Harmansa ◽

Emmanuel Caussinus ◽

Markus Affolter

Keyword(s):

Cell Migration ◽

Myosin Ii ◽

Branching Morphogenesis ◽

Stalk Cell ◽

Germ Band ◽

Tracheal System ◽

Tip Cell ◽

Dorsal Branch ◽

Cell Intercalation ◽

Tip Cells

AbstractThe Drosophila tracheal system consists of an interconnected network of monolayered epithelial tubes that ensures oxygen transport in the larval and adult body. During tracheal dorsal branch (DB) development, individual DBs elongate as a cluster of cells, led by tip cells at the front and trailing cells in the rear. Branch elongation is accompanied by extensive cell intercalation and cell lengthening of the trailing stalk cells. While cell intercalation is governed by Myosin II (MyoII)-dependent forces during tissue elongation in the Drosophila embryo leading to germ-band extension, it remained unclear whether MyoII plays a similar active role during tracheal branch elongation and intercalation. Here, we use a nanobody-based approach to selectively knock-down MyoII in tracheal cells. Our data shows that despite the depletion of MyoII function, tip cells migration and stalk cell intercalation (SCI) proceeds at a normal rate. Therefore, our data confirms a model in which DB elongation and SCI in the trachea occurs as a consequence of tip cell migration, which produces the necessary forces for the branching process.Summary statementBranch elongation during Drosophila tracheal development mechanistically resembles MyoII-independent collective cell migration; tensile forces resulting from tip cell migration are reduced by cell elongation and passive stalk cell intercalation.AbbreviationsDBDorsal branchDCDorsal closureE-CadE-CadherinGBEGerm-band extensionMRLCMyosin regulatory light chainMyoIIMyosin IISCIstalk cell intercalationSqhSpaghetti squashSxllSex lethalTCTip cellTrTracheomere

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The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms22116074 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6074

Author(s):

Maciej Danielewski ◽

Agnieszka Matuszewska ◽

Adam Szeląg ◽

Tomasz Sozański

Keyword(s):

Transcription Factors ◽

Cholesterol Metabolism ◽

Binding Protein ◽

Regulatory Element ◽

Cholesterol Homeostasis ◽

Lipid Lowering ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Cell Functions ◽

The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

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Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

Scientific Reports ◽

10.1038/s41598-019-55203-w ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Yildiz Koca ◽

Benjamin E. Housden ◽

William J. Gault ◽

Sarah J. Bray ◽

Marek Mlodzik

Keyword(s):

Notch Signaling ◽

Cell Fate ◽

Planar Cell Polarity ◽

Egf Receptor ◽

Control Cell ◽

Loss Of Function ◽

Egfr Signaling ◽

Specific Expression ◽

Egfr Signaling Pathway ◽

Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

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Rudhira/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling

Molecular Biology of the Cell ◽

10.1091/mbc.e18-08-0484 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1437-1450 ◽

Cited By ~ 3

Author(s):

Divyesh Joshi ◽

Maneesha S. Inamdar

Keyword(s):

Cell Migration ◽

Intermediate Filaments ◽

Cross Talk ◽

Control Cell ◽

The Novel ◽

Mouse Development ◽

Cytoskeleton Organization ◽

Sprouting Angiogenesis ◽

Promote Cell Migration ◽

Necessary And Sufficient

Blood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and is implicated in metastatic disease. Here, we report that Rudhira mediates cytoskeleton organization and dynamics during EC migration. Rudhira binds to both microtubules (MTs) and vimentin intermediate filaments (IFs) and stabilizes MTs. Rudhira depletion impairs cytoskeletal cross-talk, MT stability, and hence focal adhesion disassembly. The BCAS3 domain of Rudhira is necessary and sufficient for MT-IF cross-linking and cell migration. Pharmacologically restoring MT stability rescues gross cytoskeleton organization and angiogenic sprouting in Rudhira-depleted cells. Our study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. Targeting Rudhira could allow tissue-restricted cytoskeleton modulation to control cell migration and angiogenesis in development and disease.

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RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

Journal of Experimental Medicine ◽

10.1084/jem.20120565 ◽

2012 ◽

Vol 209 (13) ◽

pp. 2409-2422 ◽

Cited By ~ 77

Author(s):

Heiyoun Jung ◽

Benjamin Hsiung ◽

Kathleen Pestal ◽

Emily Procyk ◽

David H. Raulet

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Stress Responses ◽

Transcriptional Activation ◽

Posttranscriptional Regulation ◽

Cellular Proliferation ◽

Control Cell ◽

T Cell Subsets ◽

Cell Cycle Entry

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.

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Dietary lipids and gene expression

Biochemical Society Transactions ◽

10.1042/bst0320999 ◽

2004 ◽

Vol 32 (6) ◽

pp. 999-1002 ◽

Cited By ~ 24

Author(s):

H.M. Roche

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Transcription Factors ◽

Fatty Acid ◽

Regulatory Element ◽

Nuclear Factor Κb ◽

Dietary Lipids ◽

Dietary Fatty Acids ◽

Dietary Fatty Acid ◽

The Metabolic Syndrome

Nutrition is a key environmental factor that is particularly involved in the pathogenesis and progression of several polygenic, diet-related diseases. Nutrigenomics refers to the interaction between nutrition and the human genome. Dietary fatty acids interact with multiple nutrient-sensitive transcription factors. This explains the molecular basis of some of the health effects associated with altered dietary fatty acid composition. The metabolic syndrome is a very common condition, characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and is associated with a greater risk of cardiovascular disease. Several lines of evidence suggest that the interaction between nutrient-derived metabolic stressors and pro-inflammatory signals play an important role in the aetiology of insulin resistance and the development of the metabolic syndrome. This paper will address the interaction between several nutrient-sensitive transcription factors, including SREBP (sterol-regulatory-element-binding protein) and NFκB (nuclear factor κB), demonstrating how this interaction may be altered with dietary fatty acid interventions.

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Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes

Journal of the American Society of Nephrology ◽

10.1681/asn.2020081177 ◽

2021 ◽

pp. ASN.2020081177

Author(s):

Jingping Yang ◽

Difei Zhang ◽

Masaru Motojima ◽

Tsutomu Kume ◽

Qing Hou ◽

...

Keyword(s):

Transcriptional Regulation ◽

Transcription Factors ◽

Animal Models ◽

Cell Fate ◽

Control Cell ◽

Transgenic Animal ◽

Animal Models Of Disease ◽

Super Enhancer ◽

Models Of Disease ◽

Human Glomerulus

BackgroundTranscriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood.MethodsThe distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance.ResultsSuperenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish.ConclusionsFOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs’ regulatory roles in glomeruli transcription programs.

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EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm

Development ◽

10.1242/dev.122.11.3355 ◽

1996 ◽

Vol 122 (11) ◽

pp. 3355-3362 ◽

Cited By ~ 21

Author(s):

L. Gabay ◽

H. Scholz ◽

M. Golembo ◽

A. Klaes ◽

B.Z. Shilo ◽

...

Keyword(s):

Transcription Factors ◽

Target Genes ◽

Egf Receptor ◽

Protein A ◽

Drosophila Embryo ◽

Cell Fates ◽

Secondary Target ◽

Graded Activity ◽

Definition Of

The induction of different cell fates along the dorsoventral axis of the Drosophila embryo requires a graded activity of the EGF receptor tyrosine kinase (DER). Here we have identified primary and secondary target genes of DER, which mediate the determination of discrete ventral cell fates. High levels of DER activation in the ventralmost cells trigger expression of the transcription factors encoded by ventral nervous system defective (vnd) and pointed P1 (pntPl). Concomitant with the induction of pntP1, high levels of DER activity lead to inactivation of the Yan protein, a transcriptional repressor of Pointed-target genes. These two antagonizing transcription factors subsequently control the expression of secondary target genes such as otd, argos and tartan. The simultaneous effects of the DER pathway on pntP1 induction and Yan inactivation may contribute to the definition of the border of the ventralmost cell fates.

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