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Abigail Harris, Pam Siggers, Silvia Corrochano, Nick Warr, Danielle Sagar, Daniel T Grimes, Makoto Suzuki, Rebecca D Burdine, Feng Cong, Bon-Kyoung Koo, Hans Clevers, Isabelle Stévant, Serge Nef, Sara Wells, Raja Brauner, Bochra Ben Rhouma, Neïla Belguith, Caroline Eozenou, Joelle Bignon-Topalovic, Anu Bashamboo, Ken McElreavey, Andy Greenfield
Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determination partly by opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development by inhibiting SRY-SOX9-FGF9. The molecular basis of this mutual antagonism is unclear. Here we show that ZNRF3, a WNT signaling antagonist and direct target of RSPO1-mediated inhibition, is required for sex determination in mice. XY mice lacking ZNRF3 exhibit complete or partial gonadal sex reversal, or related defects...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Chen-Wei Hsu, You-Jiun Pan, Yan-Wei Wang, Sok-Keng Tong, Bon-Chu Chung
Zebrafish gonadal sexual differentiation is an important but poorly understood subject. The difficulty in investigating zebrafish sexual development lies in its sex determination plasticity, the lack of morphological tools to distinguish juvenile females from males, and the lack of sex chromosomes in laboratory strains. Zebrafish sexual differentiation starts at around 8 days post-fertilization when germ cells start to proliferate. The number of germ cells determines the future sex of the gonad. Gonads with more germ cells differentiate into ovaries, whereas a reduced germ cell number leads to male-biased sexual differentiation...
January 31, 2018: General and Comparative Endocrinology
Lot Snijders Blok, Erik Madsen, Jane Juusola, Christian Gilissen, Diana Baralle, Margot R F Reijnders, Hanka Venselaar, Céline Helsmoortel, Megan T Cho, Alexander Hoischen, Lisenka E L M Vissers, Tom S Koemans, Willemijn Wissink-Lindhout, Evan E Eichler, Corrado Romano, Hilde Van Esch, Connie Stumpel, Maaike Vreeburg, Eric Smeets, Karin Oberndorff, Bregje W M van Bon, Marie Shaw, Jozef Gecz, Eric Haan, Melanie Bienek, Corinna Jensen, Bart L Loeys, Anke Van Dijck, A Micheil Innes, Hilary Racher, Sascha Vermeer, Nataliya Di Donato, Andreas Rump, Katrina Tatton-Brown, Michael J Parker, Alex Henderson, Sally A Lynch, Alan Fryer, Alison Ross, Pradeep Vasudevan, Usha Kini, Ruth Newbury-Ecob, Kate Chandler, Alison Male, Sybe Dijkstra, Jolanda Schieving, Jacques Giltay, Koen L I van Gassen, Janneke Schuurs-Hoeijmakers, Perciliz L Tan, Igor Pediaditakis, Stefan A Haas, Kyle Retterer, Patrick Reed, Kristin G Monaghan, Eden Haverfield, Marvin Natowicz, Angela Myers, Michael C Kruer, Quinn Stein, Kevin A Strauss, Karlla W Brigatti, Katherine Keating, Barbara K Burton, Katherine H Kim, Joel Charrow, Jennifer Norman, Audrey Foster-Barber, Antonie D Kline, Amy Kimball, Elaine Zackai, Margaret Harr, Joyce Fox, Julie McLaughlin, Kristin Lindstrom, Katrina M Haude, Kees van Roozendaal, Han Brunner, Wendy K Chung, R Frank Kooy, Rolph Pfundt, Vera Kalscheuer, Sarju G Mehta, Nicholas Katsanis, Tjitske Kleefstra
Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy...
August 6, 2015: American Journal of Human Genetics
Jen-Chieh Lin, Shing Hu, Pei-Hung Ho, Hwei-Jan Hsu, John H Postlethwait, Bon-chu Chung
HSD3B catalyzes the synthesis of δ4 steroids such as progesterone in the adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes. Our phylogenetic and conserved synteny analyses showed that the tandemly duplicated human HSD3B1 and HSD3B2 genes are coorthologs of zebrafish hsd3b1 on chromosome 9 (Dre9), whereas the gene called hsd3b2 resides on Dre20 in an ancestral chromosome segment, from which its ortholog was lost in the tetrapod lineage...
August 2015: Endocrinology
Caroline Vignet, Lucette Joassard, Laura Lyphout, Tiphaine Guionnet, Manon Goubeau, Karyn Le Menach, François Brion, Olivier Kah, Bon-Chu Chung, Hélène Budzinski, Marie-Laure Bégout, Xavier Cousin
The release of polycyclic aromatic hydrocarbons (PAHs) into the environment has increased very substantially over the last decades. PAHs are hydrophobic molecules which can accumulate in high concentrations in sediments acting then as major secondary sources. Fish contamination can occur through contact or residence nearby sediments or though dietary exposure. In this study, we analyzed certain physiological traits in unexposed fish (F1) issued from parents (F0) exposed through diet to three PAH mixtures at similar and environmentally relevant concentrations but differing in their compositions...
November 2015: Environmental Science and Pollution Research International
Swamy K Tripurani, Gabbine Wee, Kyung-Bon Lee, George W Smith, Lei Wang, Jianboyao
Factor in the germline alpha (FIGLA) is an oocyte-specific basic helix-loop-helix transcription factor essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. Here we report the characterization of bovine FIGLA gene and its regulation during early embryogenesis. Bovine FIGLA mRNA expression is restricted to gonads and is detected in fetal ovaries harvested as early as 90 days of gestation. FIGLA mRNA and protein are abundant in germinal vesicle and metaphase II stage oocytes, as well as in embryos from pronuclear to eight-cell stage but barely detectable at morula and blastocyst stages, suggesting that FIGLA might be a maternal effect gene...
2013: PloS One
Jui-Hsia Weng, Ming-Ren Liang, Chien-Han Chen, Sok-Keng Tong, Tzu-Chiao Huang, Sue-Ping Lee, Yet-Ran Chen, Chao-Tsen Chen, Bon-Chu Chung
Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polymerization by binding a microtubule plus end-tracking protein, cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish embryonic extract using a P5 photoaffinity probe conjugated to diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and changed it into an extended conformation...
October 2013: Nature Chemical Biology
Che-Yi Lin, Cheng-Chen Huang, Wen-Der Wang, Chung-Der Hsiao, Ching-Feng Cheng, Yi-Ting Wu, Yu-Fen Lu, Sheng-Ping L Hwang
The coordinated migration of bilateral cardiomyocytes and the formation of the cardiac cone are essential for heart tube formation. We investigated gene regulatory mechanisms involved in myocardial migration, and regulation of the timing of cardiac cone formation in zebrafish embryos. Through screening of zebrafish treated with ethylnitrosourea, we isolated a mutant with a hypomorphic allele of mil (s1pr2)/edg5, called s1pr2(as10) (as10). Mutant embryos with this allele expressed less mil/edg5 mRNA and exhibited cardia bifida prior to 28 hours post-fertilization...
2013: PloS One
Jacqueline Boultwood, Bon Ham Yip, Chaitanya Vuppusetty, Andrea Pellagatti, James S Wainscoat
Patients with the 5q- syndrome and Diamond-Blackfan anemia (DBA) suffer from a severe macrocytic anemia. The 5q- syndrome and DBA are disorders of aberrant ribosome biogenesis (ribosomopathies) and haploinsufficiency of the ribosomal protein genes RPS14 and RPS19, respectively, underlies the anemia found in these disorders. Erythroblasts obtained from patients with the 5q- syndrome and DBA show impaired mRNA translation and this defect in translation may represent a potential therapeutic target in these ribosomopathies...
January 2013: Advances in Biological Regulation
François Brion, Yann Le Page, Benjamin Piccini, Olivier Cardoso, Sok-Keng Tong, Bon-chu Chung, Olivier Kah
The tg(cyp19a1b-GFP) transgenic zebrafish expresses GFP (green fluorescent protein) under the control of the cyp19a1b gene, encoding brain aromatase. This gene has two major characteristics: (i) it is only expressed in radial glial progenitors in the brain of fish and (ii) it is exquisitely sensitive to estrogens. Based on these properties, we demonstrate that natural or synthetic hormones (alone or in binary mixture), including androgens or progestagens, and industrial chemicals induce a concentration-dependent GFP expression in radial glial progenitors...
2012: PloS One
Susan Du, Bruce W Draper, Marina Mione, Cecilia B Moens, Ashley Bruce
The T-box transcription factor Eomesodermin (Eomes) has been implicated in patterning and morphogenesis in frog, fish and mouse. In zebrafish, one of the two Eomes homologs, Eomesa, has been implicated in dorsal-ventral patterning, epiboly and endoderm specification in experiments employing over-expression, dominant-negative constructs and antisense morpholino oligonucleotides. Here we report for the first time the identification and characterization of an Eomesa mutant generated by TILLING. We find that Eomesa has a strictly maternal role in the initiation of epiboly, which involves doming of the yolk cell up into the overlying blastoderm...
February 1, 2012: Developmental Biology
Swamy K Tripurani, Kyung-Bon Lee, Gabbine Wee, George W Smith, Jianbo Yao
BACKGROUND: Oocyte-derived maternal RNAs drive early embryogenesis when the newly formed embryo is transcriptionally inactive. Recent studies in zebrafish have identified the role of microRNAs during the maternal-to-embryonic transition (MET). MicroRNAs are short RNAs that bind to the 3' UTR of target mRNAs to repress their translation and accelerate their decay. Newborn ovary homeobox gene (NOBOX) is a transcription factor that is preferentially expressed in oocytes and essential for folliculogenesis in mice...
2011: BMC Developmental Biology
Mélanie Vosges, Yann Le Page, Bon-Chu Chung, Yves Combarnous, Jean-Marc Porcher, Olivier Kah, François Brion
Until now, studies dedicated to the actions of endocrine disrupting chemicals (EDCs) on the reproductive axis have been concerned with their effects at the gonadal level leaving their actions on neuroendocrine circuits controlling reproduction virtually unexplored. In vertebrates, gonadotropin-releasing hormone (GnRH) is the key factor controlling the activity of the reproductive axis. The development and functioning of GnRH neurons are finely tuned by a series of factors, notably sex steroids, making these neurons potential targets of EDCs, notably in aquatic species...
September 15, 2010: Aquatic Toxicology
Sok-Keng Tong, Hwei-Jan Hsu, Bon-chu Chung
The zebrafish is a popular model for genetic analysis and its sex differentiation has been the focus of attention for breeding purposes. Despite numerous efforts, very little is known about the mechanism of zebrafish sex determination. The lack of discernible sex chromosomes and the difficulty of distinguishing the sex of juvenile fish are two major obstacles that hamper the progress in such studies. To alleviate these problems, we have developed a scheme involving methyltestosterone treatment followed by natural mating to generate fish with predictable sex trait...
August 15, 2010: Developmental Biology
Hwei-Jan Hsu, Jen-Chieh Lin, Bon-chu Chung
Zebrafish has been used increasingly as a good animal model for a number of studies. To facilitate the use of this zebrafish model, the current report put emphasis on the study of two steroidogenic genes: cyp11a1 and hsd3b. These two genes encode enzymes that catalyze the first two steps of the steroidogenic pathway, and both enzymes are important for the synthesis of all steroids. Zebrafish cyp11a1 and hsd3b genes are expressed in the same cells in the gonads and interrenal gland. The interrenal gland is the counterpart of mammalian adrenal; it is located inside the head kidney and is developed parallel to the development of the pronephros...
November 27, 2009: Molecular and Cellular Endocrinology
Olivier Kah, Elisabeth Pellegrini, Karen Mouriec, Nicolas Diotel, Isabelle Anglade, Colette Vaillant, Marie-Lise Thieulant, Sok-Keng Tong, François Brion, Bon-Chu Chung, Farzad Pakdel
In contrast to other vertebrates, in which the adult brain shows limited adult neurogenesis, teleost fish exhibit an unparalleled capacity to generate new neurons as adults, suggesting that their brains present a highly permissive environment for the maintenance and proliferation of adult progenitors. Here, we examine the hypothesis that one of the factors permitting establishment of this favourable environment is estradiol. Indeed, recent data showed that radial glial cells strongly expressed one of two aromatase duplicated genes...
2009: Journal de la Société de Biologie
Sok-Keng Tong, Karen Mouriec, Ming-Wei Kuo, Elisabeth Pellegrini, Marie-Madeleine Gueguen, François Brion, Olivier Kah, Bon-chu Chung
Aromatase is an enzyme that catalyzes the synthesis of estrogen in gonads and brain. Teleost fish express aromatase (AroB) strongly in the brain facilitating its detailed examination. To understand the function of AroB in the brain, we generated transgenic zebrafish that expresses green fluorescent protein (GFP) driven by the brain aromatase cyp19a1b promoter. GFP was found in the radial glial cells of transgenic larvae and adult fish that overlap with AroB immunoreactivity in the correct temporal and spatial pattern...
February 2009: Genesis: the Journal of Genetics and Development
Takamasa Mizoguchi, Toshiaki Izawa, Atsushi Kuroiwa, Yutaka Kikuchi
In zebrafish development, Nodal signaling is critical for the induction of endoderm and mesoderm. Three transcription factors downstream of Nodal, Bonnie and Clyde (Bon), Faust (Fau)/Gata5 and Casanova (Cas), are required for endoderm induction. However, it is not yet fully understood how the Nodal signaling pathway regulates the decision process of endoderm and mesoderm induction. In this study, we focused on Fgf signaling, downstream of Nodal signaling, during endoderm induction. We found that activation of Fgf signaling decreases the number of cas-expressing endodermal cells...
December 15, 2006: Developmental Biology
Ran Song, Bon-Kyoung Koo, Ki-Jun Yoon, Mi-Jeong Yoon, Kyeong-Won Yoo, Hyun-Taek Kim, Hyeon-Jeong Oh, Yoon-Young Kim, Jin-Kwan Han, Cheol-Hee Kim, Young-Yun Kong
Mutations in Drosophila neuralized (Dneur) result in a variety of developmental defects that closely resemble those of Notch mutants and other Notch pathway mutants. However, mice with disrupted neur1 do not show any aberrant cell fate specifications in neurogenesis and somitogenesis. Thus, we speculated that other vertebrate neur homolog(s) might compensate for loss of the neur gene. Here, we report the paralog of mouse Neur1, named Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta...
November 24, 2006: Journal of Biological Chemistry
Kyeong-Won Yoo, Eun-Hye Kim, Seung-Hyun Jung, Myungchull Rhee, Bon-Kyoung Koo, Ki-Jun Yoon, Young-Yun Kong, Cheol-Hee Kim
Notch signaling has an evolutionarily conserved function for cell fate determination and stem cell maintenance. Previously, we identified a novel component of the Notch signaling pathway in zebrafish, mind bomb, which encodes an E3 ubiquitin ligase essential for Notch signal activation. Further studies showed that Mind bomb(-/-) mouse embryos exhibited pan-Notch phenotypes in various tissues, suggesting that Mind bomb function is conserved in mammals. Therefore we sought to understand the various molecular partners of Mind bomb using yeast two-hybrid screening...
August 7, 2006: FEBS Letters
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