Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.

RNA-binding proteins are critically involved in the post-transcriptional control of gene expression during embryonic development and in adult life, contributing to regulating cell differentiation and maintaining tissue homeostasis. Compared to the relatively well documented functions of transcription factors, the regulatory roles of RNA-binding proteins in muscle development and function remain largely elusive. However, deficiency of many RNA-binding proteins has been associated with muscular defects, neuromuscular disorders and heart diseases, such as myotonic dystrophy, amyotrophic lateral sclerosis, and cardiomyopathy.

Knockout of rbm24a and rbm24b genes in zebrafish impairs skeletal and cardiac muscle integrity and function during development.

Backgound: Skeletal and cardiac muscles are contractile tissues whose development and function are dependent on genetic programs that must be precisely orchestrated in time and space. In addition to transcription factors, RNA-binding proteins tightly regulate gene expression by controlling the fate of RNA transcripts, thus specific proteins levels within the cell. Rbm24 has been identified as a key player of myogenesis and cardiomyogenesis in several vertebrates, by controlling various aspects of post-transcriptional regulation, including pre-mRNA alternative splicing and mRNA stabilization.

Canonical and Non-Canonical Wnt Signaling Generates Molecular and Cellular Asymmetries to Establish Embryonic Axes.

The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on β-catenin regulates the patterning of dorsoventral, anteroposterior, and left-right axes.

Interplay of RNA-binding proteins controls germ cell development in zebrafish.

The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants, called germ plasm, confer germline fate in the early embryo. Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development. RNA-binding proteins, acting in concert with other germ plasm components, play essential roles in the organization of the germ plasm and the specification, migration, maintenance, and differentiation of primordial germ cells.

RNA-Binding Proteins in Cardiomyopathies.

The post-transcriptional regulation of gene expression plays an important role in heart development and disease. Cardiac-specific alternative splicing, mediated by RNA-binding proteins, orchestrates the isoform switching of proteins that are essential for cardiomyocyte organization and contraction. Dysfunctions of RNA-binding proteins impair heart development and cause the main types of cardiomyopathies, which represent a heterogenous group of abnormalities that severely affect heart structure and function.

RNA-Binding Proteins as Critical Post-Transcriptional Regulators of Cardiac Regeneration.

Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction.

IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification.

Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction.

Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure.

Gastrulation and neurulation are successive morphogenetic processes that play key roles in shaping the basic embryonic body plan. Importantly, they operate through common cellular and molecular mechanisms to set up the three spatially organized germ layers and to close the neural tube. During gastrulation and neurulation, convergent extension movements driven by cell intercalation and oriented cell division generate major forces to narrow the germ layers along the mediolateral axis and elongate the embryo in the anteroposterior direction.

Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration.

RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level. They play major roles in the tissue- and stage-specific expression of protein isoforms as well as in the maintenance of protein homeostasis. The inner ear is a bi-functional organ, with the cochlea and the vestibular system required for hearing and for maintaining balance, respectively.

Planar cell polarity regulators in asymmetric organogenesis during development and disease.

The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six "core" proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.

RBM24 in the Post-Transcriptional Regulation of Cancer Progression: Anti-Tumor or Pro-Tumor Activity?

RNA-binding proteins are critical post-transcriptional regulators of gene expression. They are implicated in a wide range of physiological and pathological processes by modulating nearly every aspect of RNA metabolisms. Alterations in their expression and function disrupt tissue homeostasis and lead to the occurrence of various cancers.

Circumventing Zygotic Lethality to Generate Maternal Mutants in Zebrafish.

Maternal gene products accumulated during oogenesis are essential for supporting early developmental processes in both invertebrates and vertebrates. Therefore, understanding their regulatory functions should provide insights into the maternal control of embryogenesis. The CRISPR/Cas9 genome editing technology has provided a powerful tool for creating genetic mutations to study gene functions and developing disease models to identify new therapeutics.

The Adaptor Protein Lurap1 Is Required for Cell Cohesion during Epiboly Movement in Zebrafish.

Cell adhesion and polarized cellular behaviors play critical roles in a wide variety of morphogenetic events. In the zebrafish embryo, epiboly represents an important process of epithelial morphogenesis that involves differential cell adhesion and dynamic cell shape changes for coordinated movements of different cell populations, but the underlying mechanism remains poorly understood. The adaptor protein Lurap1 functions to link myotonic dystrophy kinase-related Rac/Cdc42-binding kinase with MYO18A for actomyosin retrograde flow in cell migration.

RNA-Binding Proteins in the Post-transcriptional Control of Skeletal Muscle Development, Regeneration and Disease.

Embryonic myogenesis is a temporally and spatially regulated process that generates skeletal muscle of the trunk and limbs. During this process, mononucleated myoblasts derived from myogenic progenitor cells within the somites undergo proliferation, migration and differentiation to elongate and fuse into multinucleated functional myofibers. Skeletal muscle is the most abundant tissue of the body and has the remarkable ability to self-repair by re-activating the myogenic program in muscle stem cells, known as satellite cells.

Rapid generation of maternal mutants via oocyte transgenic expression of CRISPR-Cas9 and sgRNAs in zebrafish.

Maternal products are exclusive factors to drive oogenesis and early embryonic development. As disrupting maternal gene functions is either time-consuming or technically challenging, early developmental programs regulated by maternal factors remain mostly elusive. We provide a transgenic approach to inactivate maternal genes in zebrafish primary oocytes.

Syne2b/Nesprin-2 Is Required for Actin Organization and Epithelial Integrity During Epiboly Movement in Zebrafish.

Syne2b/nesprin-2 is a giant protein implicated in tethering the nucleus to the cytoskeleton and plays an important role in maintaining cellular architecture. Epiboly is a conserved morphogenetic movement that involves extensive spreading and thinning of the epithelial blastoderm to shape the embryo and organize the three germ layers. Dynamic cytoskeletal organization is critical for this process, but how it is regulated remains elusive.

Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration.

Skeletal muscle has a remarkable capacity of regeneration after injury, but the regulatory network underlying this repair process remains elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and the maintenance of tissue homeostasis and plasticity. Rbm24 regulates myogenic differentiation during early development, but its implication in adult muscle is poorly understood.

Decoding Dishevelled-Mediated Wnt Signaling in Vertebrate Early Development.

Dishevelled proteins are key players of Wnt signaling pathways. They transduce Wnt signals and perform cellular functions through distinct conserved domains. Due to the presence of multiple paralogs, the abundant accumulation of maternal transcripts, and the activation of distinct Wnt pathways, their regulatory roles during vertebrate early development and the mechanism by which they dictate the pathway specificity have been enigmatic and attracted much attention in the past decades.

RNA-Binding Protein Rbm24 as a Multifaceted Post-Transcriptional Regulator of Embryonic Lineage Differentiation and Cellular Homeostasis.

RNA-binding proteins control the metabolism of RNAs at all stages of their lifetime. They are critically required for the post-transcriptional regulation of gene expression in a wide variety of physiological and pathological processes. Rbm24 is a highly conserved RNA-binding protein that displays strongly regionalized expression patterns and exhibits dynamic changes in subcellular localization during early development.

Rbm24 controls poly(A) tail length and translation efficiency of mRNAs in the lens via cytoplasmic polyadenylation.

Lens transparency is established by abundant accumulation of crystallin proteins and loss of organelles in the fiber cells. It requires an efficient translation of lens messenger RNAs (mRNAs) to overcome the progressively reduced transcriptional activity that results from denucleation. Inappropriate regulation of this process impairs lens differentiation and causes cataract formation.

The regulatory proteins DSCR6 and Ezh2 oppositely regulate Stat3 transcriptional activity in mesoderm patterning during development.

Embryonic cell fate specification and axis patterning requires integration of several signaling pathways that orchestrate region-specific gene expression. The transcription factor signal transducer and activator of transcription 3 (Stat3) plays important roles during early development, but it is unclear how Stat3 is activated. Here, using as a model, we analyzed the post-translational regulation and functional consequences of Stat3 activation in dorsoventral axis patterning.

Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR/Cas9.

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes.

Collagen triple helix repeat containing 1a (Cthrc1a) regulates cell adhesion and migration during gastrulation in zebrafish.

Cell adhesion and migration are key cell behaviours during gastrulation in early embryos and metastasis in cancers. Cthrc1 is a secreted protein highly conserved among vertebrates; it is upregulated in injured and diseased arteries, as well as in malignant cancers. There is increasing evidence showing that its expression and activity are associated with cancer progression and inflammatory diseases.