Vladimir P. Korzh

International Institute of Molecular and Cell Biology

The voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs of the zebrafish. The functional tetramer consists of an electrically active subunit (Kcnb1, Kv2.1) and a modulatory silent subunit (Kcng4b, Kv6.4). The two mutations in zebrafish kcng4b - kcng4b-C1 and kcng4b-C2 (Gasanov et al., 2021) - ha...

The brain ventricular system (BVS) consists of the brain ventricles and channels filled with cerebrospinal fluid (CSF). Disturbance of CSF flow has been linked to neurodegenerative diseases including hydrocephalus, which manifests as an expansion of the BVS. These relatively common developmental disorders have been observed in humans and domesticat...

Background: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, inc...

The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing E...

Autism spectrum disorders (ASDs) are characterized by abnormal behavioral traits arising from neural circuit dysfunction. While a number of genes have been implicated in ASDs, in most cases, a clear understanding of how mutations in these genes lead to circuit dysfunction and behavioral abnormality is absent. The autism susceptibility candidate 2 (...

The pancreas development depends on complex regulation of several signaling pathways, including the Hedgehog (Hh) signaling via a receptor complex component, Smoothened, which deficiency blocks the Hh signaling. Such a defect in birds and mammals results in an annular pancreas. We showed that in developing zebrafish, the mutation of Smoothened or i...

We developed an ex silico evolutionary‐based systematic synteny approach to define and name the duplicated genes in vertebrates. The first convention for the naming of genes relied on historical precedent, the order in the human genome, and mutant phenotypes in model systems. However, total‐genome duplication that resulted in teleost genomes requir...

Activation of the embryonic genome during development represents a major developmental transition in all species. The history of its exploration began in the 1950s–1960s, when this idea was put forward and proven experimentally by Alexander Neyfakh. He observed the aberrant development of fish embryos upon X-ray irradiation and noted the different...

Development of the brain ventricular system of vertebrates and the molecular mechanisms involved are not fully understood. The developmental genes expressed in the elements of the brain ventricular system such as the ependyma and circumventricular organs act as molecular determinants of cell adhesion critical for the formation of brain ventricular...

The atrioventricular canal (AVC) is an essential feature of the heart, which separates the atrium from the ventricle. During heart morphogenesis, it is a hub of molecular processes necessary for distinguishing heart regions; most importantly, for the formation of the AV conduction system and cardiac valves. To better understand the molecular proces...

Current methods of CRISPR-Cas9-mediated site-specific mutagenesis create deletions and small insertions at the target site which are repaired by imprecise non-homologous end-joining. Targeting of the Cas9 nuclease relies on a short guide RNA (gRNA) corresponding to the genome sequence approximately at the intended site of intervention. We here prop...

Background: Sinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, incl...

The function of the inner ear depends on the maintenance of high concentrations of K+ ions. The slow-inactivating delayed rectifier Kv2.1/KCNB1 channel works in the inner ear in mammals. The kcnb1 gene is expressed in the otic vesicle of developing zebrafish, suggesting its role in development of the inner ear. In the present study, we found that a...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Wnt3 proteins are lipidated and glycosylated signaling molecules that play an important role in zebrafish neural patterning and brain development. However, the transport mechanism of lipid-modified Wnts through the hydrophilic extracellular environment for long-range action remains unresolved. Here we determine how Wnt3 accomplishes long-range dist...

Autism spectrum disorders (ASDs) are characterized by abnormal behavioral traits arising from neural circuit dysfunction. While a number of genes have been implicated in ASDs, in most cases, a clear understanding of how mutations in these genes lead to circuit dysfunction and behavioral abnormality is absent. The autism susceptibility candidate 2 (...

Wnt3 proteins are lipidated and glycosylated, secreted signaling molecules that play an im-portant role in zebrafish neural patterning and brain development. However, the transport mechanism of lipid-modified Wnts through the hydrophilic extracellular environment for long-range action remains unresolved. Here, we determine how Wnt3 accomplishes lon...

During the development of the central nervous system, the proliferation of neural progenitors and differentiation of neurons and glia are tightly regulated by different transcription factors and signaling cascades, such as the Wnt and Shh pathways. This process takes place in cooperation with several microRNAs, some of which evolutionarily conserve...

The initial convention to name genes relied on historical precedent, order in the human genome or mutants in model systems. However, partial duplication of genes in teleosts required naming the duplicated genes, so ohnologs adopted the 'a' or 'b' extension. Rapid advances in deciphering the zebrafish genome in relation to the human genome institute...

The circumventricular organs (CVOs) function by mediating chemical communication between blood and brain across the blood-brain barrier. Their origin and developmental mechanisms involved are not understood in enough detail due to a lack of molecular markers common for CVOs. These rather small and inconspicuous organs are found in close vicinity to...

Kv2.1 voltage‐gated potassium channels consist of two types of α‐subunits: (1) electrically‐active Kcnb1 α‐subunits and (2) silent or modulatory α‐subunits plus β‐subunits that, similar to silent α‐subunits, also regulate electrically‐active subunits. Voltage‐gated potassium channels were traditionally viewed, mainly by electrophysiologists, as reg...

Background Identifying enhancers and deciphering their putative roles represent a major step to better understand the mechanism of metazoan gene regulation, development, and the role of regulatory elements in disease. Comparative genomics and transgenic assays have been used with some success to identify critical regions that are involved in regula...

The emergence of genomics and its use in combination with high-resolution bioimaging for the study of animal development mechanisms provide scientists with information on gene sets and regulation thereof during development. This enabled the identification of the core set of transcription factors involved in the development of invertebrates and vert...

Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, thei...

The introduction of genomics into the field of developmental biology led to a vast expansion of knowledge about developmental genes and signaling mechanisms they are involved in. Unlike mammals, the zebrafish features seven Zic genes. This provides an interesting insight into Zic gene evolution. In addition, an unprecedented bioimaging capability o...

The brain ventricular system (BVS) consists of brain ventricles and channels connecting ventricles filled with cerebrospinal fluid (CSF). The disturbance of CSF flow has been linked to neurodegenerative disease including hydrocephalus, which manifests itself as an abnormal expansion of BVS. This relatively common developmental disorder has been obs...

A new Membrane Film Sensor (MFS) has been developed to measure pH of fluids. MFS comprises a polyelectrolyte multilayer film with uniformly distributed compartments (microchambers) where a fluorescent sensing dye is encapsulated. Fabricated film is sealed onto a polyethylene film for a future use. MFS was applied to report changes in golden pomfret...

In the earliest stages of animal development following fertilization, maternally deposited mRNAs direct biological processes to the point of zygotic genome activation (ZGA). These maternal mRNAs undergo cytoplasmic polyadenylation (CPA), suggesting translational control of their activation. To elucidate the biological role of CPA during embryogenes...

The circumventricular organs (CVOs) are small structures lining the cavities of brain ventricular system. They are associated with the semitransparent regions of the blood-brain barrier (BBB). Hence it is thought that CVOs mediate biochemical signaling and cell exchange between the brain and systemic blood. Their classification is still controversi...

Transgenic zebrafish (Gateways) expresses GFP in the AP, OVLT, SFO, ME, PVO, and migratory microglia. (A) anti-GFP WISH and (B) immunohistochemistry. (A,B) wholemount lateral view (eyes removed); anterior to the left. ah, adenohypophysis; ap, area postrema; c, cerebellum; cpIII, choroid plexus of III ventricle; cpIV, choroid plexus of IV ventricle;...

Mutant analysis of development of the OVLT and SFO at 48 hpf. (A,B) Frontal view and confocal cross-section of control embryo. Strong GFP expression maps the OVLT-SFO complex, which clearly separates into two parts–dorsal and ventral (white arrows). (C,D) Frontal view and confocal cross-section of ace−/− mutant embryo. The GFP expression domain cor...

The 3D projection of the anterior brain of the control Gateways embryo (48 hpf). The midline signal corresponds to the OVLT (ventral cluster) and the SFO (dorsal cluster). Corresponds to sections in Figures S1A,B.

The expression pattern of memKR in KR19 mimics that of GFP in Gateways. ap, area postrema; cp, choroid plexus; pin, pineal; rp, roof plate. Scale bar−50 μm.

The 3D projection of the anterior brain of the mib-/- mutant embryo on Gateways background (48 hpf). The dorsal cluster corresponding to the SFO is missing. Corresponds to sections in Figures S1E,F.

NFκB signaling has a pivotal role in regulation of development, innate immunity, and inflammation. Ikk2 is one of the two critical kinases that regulate the NFκB signaling pathway. While the role of Ikk2 in immunity, inflammation and oncogenesis has received attention, an understanding of the role of Ikk2 in vertebrate development has been compound...

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

The current study explored the Na⁺/K⁺-ATPase (NKA) inhibition-independent proarrhythmic mechanisms of cardiac glycosides (CGs) which are well-known NKA inhibitors. With the cytosolic Ca²⁺ chelated by EGTA and BAPTA or extracellular Ca²⁺ replaced by Ba²⁺, effects of bufadienolides (bufalin (BF) and cinobufagin (CBG)) and cardenolides (ouabain (Oua)...

Chronic heart failure is often characterized by the elevated amounts of reactive oxygen species such as hydrogen peroxide (H2O2) in the heart. Thus, it is of importance that selective release of therapeutic drugs occurs at the heart failure site to maximize therapeutic effects. In this work, functional mesoporous silica nanoparticles (MSNPs) were d...

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the poly...

The brain ventricular system is essential for neurogenesis and brain homeostasis. Its neuroepithelial lining effects these functions, but the underlying molecular pathways remain to be understood. We found that the K channels expressed in neuroepithelial cells determine formation of the ventricular system. The phenotype of a novel zebrafish mutant...

Quantification of GFP-Oct4 concentration and activity in zebrafish rescued and non-rescued embryos.Values for concentration and diffusion parameters were derived from the analysis of FCS data with the ACFs fit by two-component anomalous diffusion model. D1, D2: Diffusion coefficients of the fast and slow diffusion components, respectively. F2: Slow...

FCCS parameters of GFP-Nanog and mCherry-Oct4 in mesendoderm and ectoderm of blastula embryos (oblong stage; 3.5 hpf).Diffusion parameters values were derived from analysis of FCCS data with the ACFs and CCF fit by two-component anomalous diffusion model. D1, D2: Diffusion coefficient of the fast and slow diffusion component, respectively. α1, α2:...

FCCS parameters of GFP-Nanog and mCherry-Oct4 in mesendoderm and ectoderm of gastrula embryos (50% epiboly; 5.7 hpf).Diffusion parameters were derived from analysis of FCCS data with the ACFs and CCF fit by two-component anomalous diffusion model. D1, D2: Diffusion coefficients of the fast and slow diffusion components, respectively. α1, α2: anomal...

Quantification of GFP-Oct4 and GFP-Nanog activity in mesendoderm and ectoderm of wt and morphant zebrafish embryos.Diffusion parameters values were derived from analysis of FCS data with the ACFs fit by two-component anomalous diffusion model. D1, D2: Diffusion coefficients of the fast and slow diffusion components, respectively. F2: Slow component...

FCCS parameters of GFP-Sox32 and mCherry-Nanog in endoderm of gastrula embryos (50% epiboly; 5.7 hpf).Diffusion parameters were derived from analysis of FCCS data with the ACFs and CCF fit by two-component anomalous diffusion model. D1, D2: Diffusion coefficients of the fast and slow diffusion components, respectively. α1, α2: anomalous parameters...

List of QRT-PCR primers. Forward and reverse primers used in the qRT-PCR experiments. See Figure 6 and Figure 4—figure supplement 1. DOI: http://dx.doi.org/10.7554/eLife.11475.027

Combination therapy with high spatial and temporal resolution is highly promising for efficient medical treatment of cancer. In this study, doxorubicin (DOX) conjugated amphiphilic block copolymer with a terminal folic acid moiety was prepared, which could self-assemble into nanoparticles by encapsulating organic near-infrared (NIR) absorbing dye I...

The cardiac conduction system (CCS) propagates and coordinates the electrical excitation that originates from the pacemaker cells, throughout the heart, resulting in rhythmic heartbeat. Its defects result in life-threatening arrhythmias and sudden cardiac death. Understanding of the factors involved in the formation and function of the CCS remains...

Wnt3 is a morphogen that activates the Wnt signaling pathway and regulates a multitude of biological processes ranging from cell proliferation and cell fate specification to differentiation over embryonic induction to neural patterning. Recent studies have shown that the palmitoylation of Wnt3 by Porcupine, a membrane-bound O-acyltransferase, plays...

The boundaries of brain regions are associated with the tissue-specific secretion of ligands from different signaling pathways. The dynamics of these ligands in vivo and the impact of its disruption remain largely unknown. Using light and fluorescence microscopy for the overall imaging of the specimen and fluorescence correlation spectroscopy (FCS)...

Mutations in the gene encoding the MECP2 underlies Rett syndrome, a neurodevelopmental disorder in young females. Although reduced pain sensitivity in Rett syndrome patients and in partial MeCP2 deficient mice had been reported, these previous studies focused predominantly on motor impairments. Therefore, it is still unknown how MeCP2 is involved i...

The boundaries of brain regions are associated with the tissue-specific secretion of ligands from different signalling pathways. The dynamics of these ligands in vivo and the impact of its disruption remain largely unknown. We used light and fluorescence microscopy for the overall imaging of the specimen and fluorescence correlation spectroscopy (F...

Although near-infrared (NIR) light-absorbing organic dyes have recently been proposed for photothermal ablation of tumors, their clinical applications have often been hampered by problems such as low water solubility and minimal tissue absorption. Rapid development of nanotechnology provides various novel nanostructures to address these issues. In...

Fluorescence Correlation Spectroscopy (FCS) is a powerful technique to investigate molecular dynamics with single molecule sensitivity. In particular in the life sciences it has found widespread application using fluorescent proteins as labels. However, FCS data analysis and interpretation using fluorescent proteins remains challenging due to the o...

BDNF and its specialized receptor TrkB are expressed in the developing lateral line system of zebrafish, but their role in this organ is unknown. To tackle this problem in vivo, we used transgenic animals expressing fluorescent markers in different cell types of the lateral line and combined a BDNF gain-of-function approach by BDNF mRNA overexpress...

The advent of genomics in the study of developmental mechanisms has brought a trove of information on gene datasets and regulation during development, where the Zic family of zinc-finger proteins plays an important role. Genomic analysis of the modes of action of Zic3 in pluripotent cells demonstrated its requirement for maintenance of stem cells p...

Clusterin, a protein associated with multiple functions, is expressed in a wide variety of tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of-function approaches has yet to be performed to understand the underlying mechanisms of cl...

The blood-cerebrospinal fluid boundary is present at the level of epithelial cells of the choroid plexus. As one of the sources of the cerebrospinal fluid (CSF), the choroid plexus (CP) plays an important role during brain development and function. Its formation has been studied largely in mammalian species. Lately, progress in other model animals,...

MED13L is a component subunit of the Mediator complex, an important regulator of transcription that is highly conserved across eukaryotes. Here we report MED13L disruption in a translocation t(12;19) breakpoint of a patient with Pierre-Robin syndrome, moderate intellectual disability (ID), craniofacial anomalies, and muscular defects. The phenotype...

An NIR-triggered drug delivery system was developed by capping photo-switchable azobenzene-based rotaxane onto Au nanorod-mesoporous silica core-shell hybrids. Drug release from the nanocarrier in zebrafish embryo models could be controlled remotely under NIR irradiation, showing significant drug spreading to the adjacent tissues.

Neurulation is traditionally defined as the process of closure of the neural tube. New data have shown that the major driving forces of neurulation continue to operate with the closure of the neural tube, at least until the central canal of the neural tube has formed. Owing to this, the paper proposes to distinguish two periods of neurulation. Acco...

Neurulation is defined as a process of neural tube closure. Recent reports suggested that upon completion of this process the major factors of neurulation remain in force at least until the central canal of the neural tube is formed. Hence, an idea has been put forward to define the two periods of neurulation: early neurulation corresponds to the p...

Optogenetic methods are gaining broad recognition. The zebrafish is particularly useful for these applications as a model vertebrate due to a unique combination of translucent embryos/larvae and efficient transgenesis. Here, we describe a zebrafish model of light-induced cardiac deficiency. Upon illumination with intense green light, the membrane-t...

The evolutionarily conserved Hippo signaling pathway controls organ size by regulating cell proliferation and apoptosis and this process involves Yap1. The zebrafish Yap1 acts during neural differentiation, but its function is not fully understood. The detailed analysis of yap1 expression in proliferative regions, revealed it in the otic placode th...

The emergence of jawed vertebrates (gnathostomes) from jawless vertebrates was accompanied by major morphological and physiological innovations, such as hinged jaws, paired fins and immunoglobulin-based adaptive immunity. Gnathostomes subsequently diverged into two groups, the cartilaginous fishes and the bony vertebrates. Here we report the whole-...

Tbx2 is a member of the T-box family of transcription factors essential for embryo- and organogenesis. A deficiency in the zebrafish paralogue tbx2a causes abnormalities of the pharyngeal arches in a p53-independent manner. The pharyngeal arches are formed by derivatives of all three embryonic germ layers: endodermal pouches, mesenchymal condensati...