@article {118, title = {Fish-Ing for Enhancers in the Heart.}, journal = {Int J Mol Sci}, volume = {22}, year = {2021}, month = {2021 Apr 10}, abstract = {

Precise control of gene expression is crucial to ensure proper development and biological functioning of an organism. Enhancers are non-coding DNA elements which play an essential role in regulating gene expression. They contain specific sequence motifs serving as binding sites for transcription factors which interact with the basal transcription machinery at their target genes. Heart development is regulated by intricate gene regulatory network ensuring precise spatiotemporal gene expression program. Mutations affecting enhancers have been shown to result in devastating forms of congenital heart defect. Therefore, identifying enhancers implicated in heart biology and understanding their mechanism is key to improve diagnosis and therapeutic options. Despite their crucial role, enhancers are poorly studied, mainly due to a lack of reliable way to identify them and determine their function. Nevertheless, recent technological advances have allowed rapid progress in enhancer discovery. Model organisms such as the zebrafish have contributed significant insights into the genetics of heart development through enabling functional analyses of genes and their regulatory elements in vivo. Here, we summarize the current state of knowledge on heart enhancers gained through studies in model organisms, discuss various approaches to discover and study their function, and finally suggest methods that could further advance research in this field.

}, keywords = {Animals, Binding Sites, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart, Humans, Mutation, Transcription Factors, Zebrafish}, issn = {1422-0067}, doi = {10.3390/ijms22083914}, author = {Parisi, Costantino and Vashisht, Shikha and Winata, Cecilia Lanny} } @article {73, title = {The interaction of epithelial Ihha and mesenchymal Fgf10 in zebrafish esophageal and swimbladder development.}, journal = {Dev Biol}, volume = {359}, year = {2011}, month = {2011 Nov 15}, pages = {262-76}, abstract = {

Developmental patterning and growth of the vertebrate digestive and respiratory tracts requires interactions between the epithelial endoderm and adjacent mesoderm. The esophagus is a specialized structure that connects the digestive and respiratory systems and its normal development is critical for both. Shh signaling from the epithelium regulates related aspects of mammalian and zebrafish digestive organ development and has a prominent effect on esophageal morphogenesis. The mechanisms underlying esophageal malformations, however, are poorly understood. Here, we show that zebrafish Ihha signaling from the epithelium acting in parallel, but independently of Shh, controls epithelial and mesenchymal cell proliferation and differentiation of smooth muscles and neurons in the gut and swimbladder. In zebrafish ihha mutants, the esophageal and swimbladder epithelium is dysmorphic, and expression of fgf10 in adjacent mesenchymal cells is affected. Analysis of the development of the esophagus and swimbladder in fgf10 mutant daedalus (dae) and compound dae/ihha mutants shows that the Ihha-Fgf10 regulatory interaction is realized through a signaling feedback loop between the Ihha-expressing epithelium and Fgf10-expressing mesenchyme. Disruption of this loop further affects the esophageal and swimbladder epithelium in ihha mutants, and Ihha acts in parallel to but independently of Shha in this process. These findings contribute to the understanding of epithelial-mesenchymal interactions and highlight an interaction between Hh and Fgf signaling pathways during esophagus and swimbladder development.

}, keywords = {Air Sacs, Animals, Animals, Genetically Modified, Cell Proliferation, Embryo, Nonmammalian, Epithelium, Esophagus, Female, Fibroblast Growth Factor 10, Gastrointestinal Tract, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Green Fluorescent Proteins, Hedgehog Proteins, In Situ Hybridization, Male, Membrane Proteins, Mesoderm, Microscopy, Confocal, Mutation, Protein Binding, Receptors, Cell Surface, Signal Transduction, Zebrafish, Zebrafish Proteins}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2011.08.024}, author = {Korzh, Svitlana and Winata, Cecilia Lanni and Zheng, Weiling and Yang, Shulan and Yin, Ao and Ingham, Phillip and Korzh, Vladimir and Gong, Zhiyuan} } @article {67, title = {Development of zebrafish swimbladder: The requirement of Hedgehog signaling in specification and organization of the three tissue layers.}, journal = {Dev Biol}, volume = {331}, year = {2009}, month = {2009 Jul 15}, pages = {222-36}, abstract = {

The swimbladder is a hydrostatic organ in fish postulated as a homolog of the tetrapod lung. While lung development has been well studied, the molecular mechanism of swimbladder development is essentially uncharacterized. In the present study, swimbladder development in zebrafish was analyzed by using several molecular markers: hb9 (epithelium), fgf10a and acta2 (mesenchyme), and anxa5 (mesothelium), as well as in vivo through enhancer trap transgenic lines Et(krt4:EGFP)(sq33-2) and Et(krt4:EGFP)(sqet3) that showed strong EGFP expression in the swimbladder epithelium and outer mesothelium respectively. We defined three phases of swimbladder development: epithelial budding between 36 and 48 hpf, growth with the formation of two additional mesodermal layers up to 4.5 dpf, and inflation of posterior and anterior chambers at 4.5 and 21 dpf respectively. Similar to those in early lung development, conserved expression of Hedgehog (Hh) genes, shha and ihha, in the epithelia, and Hh receptor genes, ptc1 and ptc2, as well as fgf10a in mesenchyme was observed. By analyzing several mutants affecting Hh signaling and Ihha morphants, we demonstrated an essential role of Hh signaling in swimbladder development. Furthermore, time-specific Hh inhibition by cyclopamine revealed different requirements of Hh signaling in the formation and organization of all three tissue layers of swimbladder.

}, keywords = {Air Sacs, Animals, Antigens, Differentiation, Body Patterning, Embryo, Nonmammalian, Hedgehog Proteins, Mutation, Signal Transduction, Zebrafish, Zebrafish Proteins}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2009.04.035}, author = {Winata, Cecilia L and Korzh, Svetlana and Kondrychyn, Igor and Zheng, Weiling and Korzh, Vladimir and Gong, Zhiyuan} }