References of "Muller, Marc"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe 19 Feb. 2016 Outburst of Comet 67P/CG: An ESA Rosetta Multi-Instrument Study
Grün, E.; Agarwal, J.; Altobelli, N. et al

in Monthly Notices of the Royal Astronomical Society (2016)

On 19 Feb. 2016 nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ... [more ▼]

On 19 Feb. 2016 nine Rosetta instruments serendipitously observed an outburst of gas and dust from the nucleus of comet 67P/Churyumov-Gerasimenko. Among these instruments were cameras and spectrometers ranging from UV over visible to microwave wavelengths, in-situ gas, dust and plasma instruments, and one dust collector. At 9:40 a dust cloud developed at the edge of an image in the shadowed region of the nucleus. Over the next two hours the instruments recorded a signature of the outburst that significantly exceeded the background. The enhancement ranged from 50% of the neutral gas density at Rosetta to factors >100 of the brightness of the coma near the nucleus. Dust related phenomena (dust counts or brightness due to illuminated dust) showed the strongest enhancements (factors >10). However, even the electron density at Rosetta increased by a factor 3 and consequently the spacecraft potential changed from ˜-16 V to -20 V during the outburst. A clear sequence of events was observed at the distance of Rosetta (34 km from the nucleus): within 15 minutes the Star Tracker camera detected fast particles (˜25 m s[SUP]-1[/SUP]) while 100 μm radius particles were detected by the GIADA dust instrument ˜1 hour later at a speed of ~6 m s[SUP]-1[/SUP]. The slowest were individual mm to cm sized grains observed by the OSIRIS cameras. Although the outburst originated just outside the FOV of the instruments, the source region and the magnitude of the outburst could be determined. [less ▲]

Detailed reference viewed: 17 (5 ULg)
Full Text
Peer Reviewed
See detailToxicity of organometal halide perovskite solar cells
Babayigit, Aslihan; Ethirajan, Anitha; Muller, Marc ULg et al

in Nature Materials (2016), 15

Detailed reference viewed: 23 (5 ULg)
Full Text
Peer Reviewed
See detailAssessing the toxicity of Pb- and Sn-based perovskite solar cells in model organism Danio rerio
Babayigit, Aslihan; Dinh Duy Thanh, ULg; Ethirajan, Anitha et al

in Scientific Reports (2016), 6

Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all ... [more ▼]

Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-scale application. Aiming for the retention of favorable electro-optical properties, tin (Sn) has been considered the most likely substitute. Preliminary studies have however shown that Sn-based perovskites are highly unstable and, moreover, Sn is also enlisted as a harmful chemical, with similar concerns regarding environment and health. To bring more clarity into the appropriateness of both metals in perovskite solar cells, we provide a case study with systematic comparison regarding the environmental impact of Pb- and Sn-based perovskites, using zebrafish (Danio Rerio) as model organism. Uncovering an unexpected route of intoxication in the form of acidification, it is shown that Sn based perovskite may not be the ideal Pb surrogate. [less ▲]

Detailed reference viewed: 260 (32 ULg)
Full Text
Peer Reviewed
See detailEndocrine activity of mycotoxins and mycotoxin mixtures
Demaegdt; Daminet; Evrard et al

in Food & Chemical Toxicology (2016), 96

Detailed reference viewed: 9 (3 ULg)
Full Text
Peer Reviewed
See detailDifferences in Strength and Timing of the mtDNA Bottleneck between Zebrafish Germline and Non-germline Cells.
Otten, Auke BC; Theunissen, Tom EJ; Derhaag, Josien G et al

in Cell Reports (2016)

We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 3 106 mtDNA molecules with high ... [more ▼]

We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 3 106 mtDNA molecules with high variation between oocytes. During embryo- genesis, the mtDNA copy number decreases to $170 mtDNA molecules per primordial germ cell (PGC), a number similar to that in mammals, and to $50 per non-PGC. These occur at the same developmental stage, implying considerable variation in mtDNA copy number in (non-)PGCs of the same female, dictated by variation in the mature oocyte. The pres- ence of oocytes with low mtDNA numbers, if similar in humans, could explain how (de novo) mutations can reach high mutation loads within a single gener- ation. High mtDNA copy numbers in mature oocytes are established by mtDNA replication during oocyte development. Bottleneck differences between germ- line and non-germline cells, due to early differentia- tion of PGCs, may account for different distribution patterns of familial mutations. [less ▲]

Detailed reference viewed: 10 (3 ULg)
Full Text
Peer Reviewed
See detailEffects of microgravity simulation on zebrafish transcriptomes and bone physiology; exposure starting at 5 days post-fertilization.
Aceto, Jessica ULg; Nourizadeh-Lillabadi, Rasoul; Bradamante, Silvia et al

in NPJ Microgravity (2016), 2

Detailed reference viewed: 27 (2 ULg)
See detailPb-based versus Sn-based perovskite solar cells: Toxicity and environmental burden
Babayigit, Aslihan; Dinh Duy Thanh, ULg; Ethirajan, Anitha et al

Poster (2015, May)

Organometal halide perovskites have rapidly evolved into strong contenders to compete with silicon in the quest for low-cost photovoltaics, with their added value being solution-processability. Their ... [more ▼]

Organometal halide perovskites have rapidly evolved into strong contenders to compete with silicon in the quest for low-cost photovoltaics, with their added value being solution-processability. Their primary drawback, however, is that so far the presence of lead (Pb) is required to obtain the highly favorable electro-optical properties of the most successful perovskite crystals such as CH3NH3PbI3. Together with their tendency to degrade under the influence of humidity, and the corresponding disintegration of the unit cell, this implies that Pb compounds can be released into the environment upon failure of a perovskite module. As already known from literature, Pb is a rather toxic element causing irreversible neurological, nephrotic and hepatic damage. Hence, finding a non-harmful alternative metal, exhibiting similar electro-optical characteristics in the resulting perovskite crystal, could be the solution to improve and ultimately commercialize perovskite-based solar cells. Tin (Sn), also being a group IV metal, has been deemed the most appropriate alternative. However, Sn is also enlisted as a harmful chemical. Animal and human volunteer studies have shown that toxicity symptoms like fever, nausea, nephropathy, etc. emerge upon excessive uptake, raising question marks regarding the suitability of Sn as a more environmentally friendly alternative to Pb in perovskite solar cells. This contribution aims to make a first step towards the assessment of the environmental burden of both Pb and Sn based solar cells in the form of a toxicity study. Well-established aquatic model organisms are exposed to the appropriate degradation products, according to well-defined guidelines of the Organization for Economic Co-operation and Development (OECD). This allows a systematic comparison of Sn and Pb-containing decayed compounds regarding their potentially harmful effects on the environment, and sheds light onto the applicability of both corresponding perovskite families in large-scale photovoltaic systems. [less ▲]

Detailed reference viewed: 413 (8 ULg)
Full Text
Peer Reviewed
See detailBMP Signaling Regulates Bone Morphogenesis in Zebrafish through Promoting Osteoblast Function as Assessed by Their Nitric Oxide Production
Windhausen, Thomas ULg; Squifflet, Steeve; Renn, Jörg ULg et al

in Molecules (2015), 20

Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of ... [more ▼]

Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of proper BMP signaling before 48 h post-fertilization (hpf) for cartilage formation in the skull. Here, we focus on the involvement of the BMP pathway between 48 and 96 hpf in bone formation after 96 hpf. Using BMP inhibitors and the expression of a dominant-negative BMP receptor, we analyze whether the loss of BMP signaling affects osteoblastogenesis, osteoblast function and bone mineralization. To this end, we used the transgenic zebrafish line Tg(osterix:mCherry), detection of nitric oxide (NO) production, and alizarin red staining, respectively. We observed that inhibition of BMP signaling between 48 and 72 hpf led to a reduction of NO production and bone mineralization. Osteoblast maturation and chondrogenesis, on the other hand, seemed unchanged. Osteoblast function and bone formation were less affected when BMP signaling was inhibited between 72 and 96 hpf. These results suggest that for the onset of bone formation, proper BMP signaling between 48 and 72 hpf is crucial to ensure osteoblast function and ossification. Furthermore, detection of NO in developing zebrafish larvae appears as an early indicator of bone calcification activity. [less ▲]

Detailed reference viewed: 32 (17 ULg)
Full Text
Peer Reviewed
See detailPhenotype Classification of Zebrafish Embryos by Supervised Learning
Jeanray, Nathalie ULg; Marée, Raphaël ULg; Pruvot, Benoist et al

in PLoS ONE (2015), 10(1), 01169891-20

Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances ... [more ▼]

Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Here, we present a methodology to automatically classify brightfield images of wildtype zebrafish embryos according to their defects by using an image analysis approach based on supervised machine learning. We show that, compared to manual classification, automatic classification results in 90 to 100 % agreement with consensus voting of biological experts in nine out of eleven considered defects in 3 days old zebrafish larvae. Automation of the analysis and classification of zebrafish embryo pictures reduces the workload and time required for the biological expert and increases the reproducibility and objectivity of this classification. [less ▲]

Detailed reference viewed: 92 (23 ULg)
Full Text
Peer Reviewed
See detailEstrogenic Evaluation and Organochlorine Identification in Blubber of North Sea Harbour Porpoise (Phocoena phocoena) Stranded on the North Sea Coast
Didimo Imazaki, Pedro Henrique ULg; Brose, François ULg; Jauniaux, Thierry ULg et al

in BioMed Research International (2015), Volume 2015(Article ID 438295), 13

Thirteen individual organochlorine compounds at 3 concentrations (80, 400, and 2000 ng/mL culture medium), as well as mixtures, were assayed for the estrogen receptor (ER) activation or inhibition, using ... [more ▼]

Thirteen individual organochlorine compounds at 3 concentrations (80, 400, and 2000 ng/mL culture medium), as well as mixtures, were assayed for the estrogen receptor (ER) activation or inhibition, using a luciferase reporter gene assay (RGA). None of the PCB 138, 153, or 180 or their mixture induced a response in the RGA. o,p'-DDT was the most potent xenoestrogen fromthe DDT group, inducing a response already at 80 ng/mL. From the HCH and HCB group, only 𝛽-HCH (at 400 and 2000 ng/mL) and 𝛿-HCH (at 2000 ng/mL) displayed estrogenic activities.These 13 organochlorines were determined by GC-MS in 12 samples of North Sea harbor porpoise blubber. The PCBs were the main contaminants. Within each group, PCB 153 (6.0 × 102∼4.2 × 104 𝜇g/kg), p,p'- DDE (5.1 × 102∼8.6 × 103 𝜇g/kg), and HCB (7.6 × 101∼1.5 × 103 𝜇g/kg) were the compounds found in highest concentrations.The hormonal activity of the porpoise blubber samples was also assayed in RGA, where two samples showed estrogenic activity, seven samples showed antiestrogenic activity, and one sample showed both estrogenic and antiestrogenic activity. Our results suggest that the 13 POPs measured by GC-MS in the samples cannot explain alone the estrogenicity of the extracts. [less ▲]

Detailed reference viewed: 48 (20 ULg)
Full Text
Peer Reviewed
See detailZebrafish bone and general physiology are differently affected by hormones or changes in gravity.
Aceto, Jessica ULg; Nourizadeh-Lillabadi, Rasoul; Marée, Raphaël ULg et al

in PLoS ONE (2015), 10(6), 1-42

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire ... [more ▼]

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. [less ▲]

Detailed reference viewed: 208 (21 ULg)
Full Text
See detailEffects of some controversial food additives on zebrafish embryonic development
Dinh Duy Thanh, ULg; Voncken, Audrey; Curé, Yoann et al

Poster (2014, December 04)

Background information: There are rising concerns about potential hazardous properties of food additives, forcing legislator to tighten management policy and requiring extensive, yet animal- minimized ... [more ▼]

Background information: There are rising concerns about potential hazardous properties of food additives, forcing legislator to tighten management policy and requiring extensive, yet animal- minimized, testing strategies. The zebrafish embryo is an emerging model system for chemical testing with many advantages that made it amenable to high-throughput assays at the in vivo level. In this study, we applied a panel of tests to evaluate toxicity, particularly neurobehavioral effects, of seven substances including standard compounds and controversial food additives. Methods: Zebrafish wildtype and transgenic fluorescent embryos were exposed to different concentrations of four food additives: Sodium benzoate (SB), Monosodium glutamate (MSG), Tartrazine (TTZ), and Quinoline yellow (QY). Method validation was carried out using three other substances: Ethanol (EtOH), Dimethyl sulfoxide (DMSO), 3,4-Dichloroaniline (DCA). Morphological and lethal effects were recorded and the data were analysed to determine median lethal concentration (LC50), median effective concentration (EC50), effective concentration 10% (EC10), and teratogenic index (TI) values as well as concentration-response equations. Delayed effects of substances on larval locomotion were inspected using the light/dark challenge. Gene expression analysis was carried out using transgenic fluorescent lines. Results: LC50 values of three standard compounds (EtOH, DMSO, and DCA) reveal a high correlation with previously validated data, proving the reliability of our method. Effects of each substance on zebrafish embryonic morphology and lethality were determined as well as the corresponding concentration-response curves. Calculated toxicological indexes revealed that SB belongs to Cat.3 aquatic toxicity class, while QY is the most teratogenic substance. At EC10, all additives exhibited a delayed effect on zebrafish larval locomotion in compound-specific patterns. Observation of transgenic fluorescent embryos and locomotion analysis of hatched larvae reveal that SB could decrease the zebrafish motoneuron differentiation rate, while TTZ exhibited anti-angiogenic effects. Conclusion: Our results demonstrate that our test panel is reliable as a means to assess and categorise chemical toxicity. Also, our data suggest the need to reconsider the safety of food additives SB, TTZ, and QY as well as other controversial food additives in further studies. [less ▲]

Detailed reference viewed: 139 (9 ULg)
Full Text
Peer Reviewed
See detailDetection of nitric oxide by diaminofluorescein visualizes the skeleton in living zebrafish.
Renn, Jörg ULg; Pruvot, Benoist; Muller, Marc ULg

in Journal of Applied Ichthyology (2014), 30(4), 701706

Several in vivo stainings, such as Calcein, Alizarin Red and Quercetin are commonly used to visualize ossification in living teleost specimen. These staining techniques represent important tools for bone ... [more ▼]

Several in vivo stainings, such as Calcein, Alizarin Red and Quercetin are commonly used to visualize ossification in living teleost specimen. These staining techniques represent important tools for bone research in fish, but do not visualize cartilage. In the present study, we show that nitric oxide (NO) labelling by DAF-FM DA visualizes both bone and cartilage in vivo during zebrafish skeletogenesis. NO detection performed in Tg(osterix:mCherry) or in combination with Alizarin Red in wild-type zebrafish reveals that intense staining through NO labelling colocalizes with the appearance of osteoblasts and characterizes ossified structures. Cartilage structures are clearly distinguished in the living larvae, although the labelling is less intensive when compared to ossified structures. This method is the first and easy to handle alternative to cartilage and bone double stainings on fixed samples. In contrast to most live skeletal stainings, which only stain the mineralized bone structures, this protocol in addition allows in vivo visualization of cartilage. [less ▲]

Detailed reference viewed: 17 (6 ULg)
Full Text
Peer Reviewed
See detailFunctional study of the Ser/Arg-rich splicing factor SRSF5a during zebrafish embryonic development
Joris, Marine ULg; Muller, Marc ULg; Motte, Patrick ULg

Poster (2014, June 05)

Nuclear pre-mRNA splicing is a key process regulating gene expression in eukaryotes. Splicing consists in the removal of introns and the joining of exons within a dynamic macromolecular complex called the ... [more ▼]

Nuclear pre-mRNA splicing is a key process regulating gene expression in eukaryotes. Splicing consists in the removal of introns and the joining of exons within a dynamic macromolecular complex called the spliceosome, which consist of five small nuclear ribonucleoproteins (snRNPs) and numerous non snRNPs proteins (1). Amongst these non snRNPs proteins, the SR proteins family constituted an important group of splicing factors that are involved in constitutive and alternative splicing (2,3). SR proteins are structurally related as they are characterized by one or two RNA-recognition motifs (RRMs) in N-ter and a C-terminal domain enriched in dipeptide Ser/Arg. Phylogenetic inference using the RRM domain allowed us to identify 13 encoding genes for SR proteins in the vertebrate model organism, Danio rerio. The Zebrafish is increasingly recognized as a powerful model for the study of vertebrate embryonic development in a physiological context. The roles of SR splicing factors during animal cell differentiation and development are largely unknown. The aim of the present research is to investigate SR proteins functions during zebrafish development by using molecular and genetic approaches. In this study, we investigated the role of the SR splicing factor SRSF5a. The expression profile was determined by in situ hybridization at 24, 48 and 72 hours post-fertilization and showed SRSF5a expression mainly in brain, retina and pharyngeal arches at these stages. Furthermore, SRSF5a knock-down by morpholinos microinjection strongly suggests an important role of this specific splicing factor during eyes and brain development. In order to gain insight into the molecular function of SRSF5a, we analysed control and morphant transcriptomes using high throughput RNA sequencing. Finally, we use a complementary approach to morpholinos and generate SRSF5a mutant fishes using TALENs (Tal effector nucleases)(4,5). 1. Wahl MC, Will CL, & Luhrmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136(4):701-718. 2. Long JC & Caceres JF (2009) The SR protein family of splicing factors: master regulators of gene expression. Biochem J 417(1):15-27. 3. Graveley BR (2000) Sorting out the complexity of SR protein functions. RNA 6(9):1197-1211. 4. Moore et al. (2012) Improved Somatic Mutagenesis in Zebrafish Using Transcription Activator-Like Effector Nucleases (TALENs). Plos One 120(1):1-12. 5. Cade et al (2012) Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs. Nucleic acid research Vol 40, No 16:8001-8010. [less ▲]

Detailed reference viewed: 69 (9 ULg)
Full Text
Peer Reviewed
See detailDevelopmental defects in zebrafish for classification of EGF pathway inhibitors.
Pruvot, Benoist ULg; Curé, Yoann ULg; Djiotsa, Joachim et al

in Toxicology and Applied Pharmacology (2014), 274

Detailed reference viewed: 38 (12 ULg)
Full Text
See detailFunctional study of the Ser/Arg-rich splicing factor SRSF5a during zebrafish embryonic development.
Joris, Marine ULg; Larbuisson, Arnaud ULg; Muller, Marc ULg et al

Poster (2013, April 18)

To investigate the role of the splicing factor SRSF5a during zebrafish embryonic development, we performed SRSF5a knockdown by morpholino microinjection and we analysed control and morphant transcriptomes ... [more ▼]

To investigate the role of the splicing factor SRSF5a during zebrafish embryonic development, we performed SRSF5a knockdown by morpholino microinjection and we analysed control and morphant transcriptomes using RNA sequencing. [less ▲]

Detailed reference viewed: 69 (21 ULg)
Full Text
Peer Reviewed
See detailRemoval of natural hormones in dairy farm wastewater using reactive and sorptive materials
Cai; Phillips; Elliott et al

in Science of the Total Environment (2013), 461-462

Detailed reference viewed: 16 (9 ULg)
Full Text
Peer Reviewed
See detailFgf receptors Fgfr1a and Fgfr2 control the function of pharyngeal endoderm in late cranial cartilage development.
Larbuisson, Arnaud ULg; Dalcq, Julia ULg; Martial, Joseph ULg et al

in Differentiation; research in biological diversity (2013), 86

Cranial cartilage derives mainly from cranial neural crest cells and its formation requires fibroblast growth factor (Fgf) signaling for early differentiation and survival of developing chondrocytes as ... [more ▼]

Cranial cartilage derives mainly from cranial neural crest cells and its formation requires fibroblast growth factor (Fgf) signaling for early differentiation and survival of developing chondrocytes as well as patterning of the endodermal pouches. Here, we investigate the role of Fgf receptors in chondrocyte maturation at later stages, beyond 24hpf. Using inducible expression of a dominant-negative Fgf receptor, we show that Fgf signaling is required around 30hpf for correct cartilage formation. The receptor genes fgfr1a and fgr2 are expressed in pharyngeal endodermal pouches after 24hpf or 26hpf, respectively. Depletion of any of these two receptors by microinjection of antisense morpholinos results in severe defects in cartilage formation at 4dpf and a decrease in expression of the late chondrocyte markers barx1 and runx2b. Although endodermal pouches are correctly formed and patterned, receptor knock down leads to decreased expression of runx3, egr1 and sox9b in this tissue, while expression of fsta, coding for a secreted BMP/Tgfss inhibitor, is clearly increased. Rescue experiments revealed that each Fgfr1a or Fgfr2 receptor is able to compensate for the loss of the other. Thus, we show that minimal amounts of Fgfr1a or Fgfr2 are required to initiate a regulatory cascade in pharyngeal endoderm reducing expression of fsta, thereby allowing correct BMP signaling to the maturing chondrocytes of the head cartilage. [less ▲]

Detailed reference viewed: 42 (12 ULg)
Full Text
Peer Reviewed
See detailRunx3, Egr1 AND Sox9b form a regulatory cascade required to modulate BMP-signaling during cranial cartilage development in zebrafish.
Dalcq, Julia ULg; Pasque, Vincent; Ghaye, Aurélie ULg et al

in PLoS ONE (2012), 7(11), 50140

The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions ... [more ▼]

The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions between neural crest cells and surrounding endodermal, ectodermal and mesodermal tissues. In this study, we show that the endodermal factors Runx3 and Sox9b form a regulatory cascade with Egr1 resulting in transcriptional repression of the fsta gene, encoding a BMP antagonist, in pharyngeal endoderm. Using a transgenic line expressing a dominant negative BMP receptor or a specific BMP inhibitor (dorsomorphin), we show that BMP signaling is indeed required around 30 hpf in the neural crest cells to allow cell differentiation and proper pharyngeal cartilage formation. Runx3, Egr1, Sox9b and BMP signaling are required for expression of runx2b, one of the key regulator of cranial cartilage maturation and bone formation. Finally, we show that egr1 depletion leads to increased expression of fsta and inhibition of BMP signaling in the pharyngeal region. In conclusion, we show that the successive induction of the transcription factors Runx3, Egr1 and Sox9b constitutes a regulatory cascade that controls expression of Follistatin A in pharyngeal endoderm, the latter modulating BMP signaling in developing cranial cartilage in zebrafish. [less ▲]

Detailed reference viewed: 62 (36 ULg)