The International Journal Of Developmental Biology[JOURNAL]
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200 papers
Enhancement of neural crest formation by mechanical force in development.
Kaneshima T, Ogawa M, Yamamoto T … +5 more , Tsuboyama Y, Miyata Y, Kotani T, Okajima T, Michiue T
Int J Dev Biol · 2024 · PMID 38591691 · Publisher ↗
In vertebrate development, ectoderm is specified into neural plate (NP), neural plate border (NPB), and epidermis. Although such patterning is thought to be achieved by molecular concentration gradients, it has been reve...
In vertebrate development, ectoderm is specified into neural plate (NP), neural plate border (NPB), and epidermis. Although such patterning is thought to be achieved by molecular concentration gradients, it has been revealed, mainly by analysis, that mechanical force can regulate cell specification. During patterning, cells deform and migrate, and this applies force to surrounding tissues, shaping the embryo. However, the role of mechanical force for cell specification is largely unknown. In this study, with an aspiration assay and atomic force microscopy, we have demonstrated that tension on ectodermal cells decreases laterally from the midline in early neurula. Ectopically applied force laterally expanded the neural crest (NC) region, a derivative of the NPB, whereas force relaxation suppressed it. Furthermore, force application activated both the FGF and Wnt pathways, which are required for NC formation during neuroectodermal patterning. Taken together, mechanical force is necessary for NC formation in order to regulate signaling pathways. Furthermore, molecular signals specify the NP and generate force on neighboring tissue, the NPB, with its closure. This force activates signals, possibly determining the appropriate width of a narrow tissue, the NC.
Disrupted odontoblast differentiation and dentin dysplasia in -deficient mice.
Jiménez-Rojo L, de Vega S, Ibarretxe G … +2 more , Nakamura T, Unda FJ
Int J Dev Biol · 2024 · PMID 38591690 · Publisher ↗
Tooth formation is a process tightly regulated by reciprocal interactions between epithelial and mesenchymal tissues. These epithelial-mesenchyme interactions regulate the expression of target genes via transcription fac...
Tooth formation is a process tightly regulated by reciprocal interactions between epithelial and mesenchymal tissues. These epithelial-mesenchyme interactions regulate the expression of target genes via transcription factors. Among the regulatory elements governing this process, Epiprofin/Sp6 is a zinc finger transcription factor which is expressed in the embryonic dental epithelium and in differentiating pre-odontoblasts. knockout (-/-) mice present severe dental abnormalities, such as supernumerary teeth and enamel hypoplasia. Here, we describe dentin defects in molars and incisors of -/- mice. We observed that in the absence of Epfn, markers of early odontoblast differentiation, such as alkaline phosphatase activity, expression, and Collagen Type I deposition, are downregulated. In addition, the expression of tight and gap junction proteins was severely impaired in the predontoblastic cell layer of developing -/- molars. Altogether, our data shows that Epfn is crucial for the proper differentiation of dental mesenchymal cells towards functional odontoblasts and subsequent dentin-matrix deposition.
Estrogen signaling in development: recent insights from the zebrafish.
Wesselman HM, Wingert RA
Int J Dev Biol · 2024 · PMID 38421034 · Publisher ↗
While traditionally recognized as a sex hormone, estrogen has a potent effect on the development of tissues beyond those of the reproductive system. Estrogen synthesis enzymes and estrogen receptors are broadly expressed...
While traditionally recognized as a sex hormone, estrogen has a potent effect on the development of tissues beyond those of the reproductive system. Estrogen synthesis enzymes and estrogen receptors are broadly expressed in vertebrate tissues, further indicating their importance in various processes. These include the tissues of the zebrafish, which is a particularly suitable model for studying early development due to its rapid ontogeny and conserved genetic and cellular composition with other vertebrates. In this review, we provide readers with an overview of estrogen signaling, discuss important attributes of the zebrafish animal model with a special focus on the kidney, and explore recent insights from zebrafish studies about the roles of estrogen signaling in organogenesis across germ layer derivatives that range from the kidney to the brain and liver.
The GLI code controls HNF1A levels during foregut differentiation.
Unger L, Mathisen AF, Chera S … +2 more , Legøy TA, Ghila L
Int J Dev Biol · 2024 · PMID 38270262 · Publisher ↗
Differentiation of human induced pluripotent stem cells towards pancreatic islet endocrine cells is a complex process, involving the stepwise modulation of key developmental pathways, such as the Hedgehog signaling inhib...
Differentiation of human induced pluripotent stem cells towards pancreatic islet endocrine cells is a complex process, involving the stepwise modulation of key developmental pathways, such as the Hedgehog signaling inhibition during early differentiation stages. In tandem with this active inhibition, key transcription factors for the islet endocrine cell fate, such as HNF1A, show specific changes in their expression patterns. Here we designed a pilot study aimed at investigating the potential interconnection between HH-signaling inhibition and the increase in the HNF1A expression during early regeneration, by inducing changes in the GLI code. This unveiled a link between the two, where GLI3-R mediated Hedgehog target genes inhibition is apparently required for HNF1A efficient expression.
Developmental Biology: from genes to functional organism - news from the 3 Meeting of the Visegrád Group Society for Developmental Biology.
Trela E, Walewska A
Int J Dev Biol · 2023 · PMID 38174766 · Publisher ↗
The third meeting of the Visegrád Group Society for Developmental Biology (V4SDB) was held on September 8-10, 2023 in Warsaw, Poland. It was a continuation of previous meetings, the first organized in the Czech Republic...
The third meeting of the Visegrád Group Society for Developmental Biology (V4SDB) was held on September 8-10, 2023 in Warsaw, Poland. It was a continuation of previous meetings, the first organized in the Czech Republic in 2018 and the second in Hungary in 2021. Similarly to the previous meetings, the organizers created a friendly platform for networking and science sharing. The conference gathered an excellent group of 160 researchers working on various animal models, who during lecture and poster sessions discussed a broad range of subjects, including early embryonic development, organogenesis, genetic and epigenetic control of developmental processes, stem cells and regeneration, cellular dynamics and migration in developmental biology, and models in development and disease. Additionally, two satellite events were organized: the Young Developmental Biologists' Forum, which gave young researchers an opportunity to share and promote their work and to participate in hands-on courses, and an outreach initiative "Developmental Biology for Everyone", which presented different aspects of developmental biology to a broad audience.
Fgf8 gene regulatory network and the isthmic organizer: an evolutionary perspective.
Chandel R, Hörnblad A
Int J Dev Biol · 2024 · PMID 40053062 · Publisher ↗
The midbrain-hindbrain boundary (MHB), also known as the isthmic organizer (IsO), plays a critical role in the developmental patterning of the posterior midbrain and anterior hindbrain. Understanding the wiring of this o...
The midbrain-hindbrain boundary (MHB), also known as the isthmic organizer (IsO), plays a critical role in the developmental patterning of the posterior midbrain and anterior hindbrain. Understanding the wiring of this organizer's deeply conserved gene regulatory network is of significant interest for both evolutionary and neurodevelopmental biology. Various secreted signalling molecules and transcription factors have been identified as being important components for the formation and function of the MHB. Among these, FGF8 is considered a primary mediator of IsO activity; it directs anterior-posterior patterning and promotes the specification and maintenance of the MHB. While the core gene regulatory network governing MHB development is well-characterized, the direct interactions between key regulatory genes and the cis-regulatory elements that control their spatiotemporal expression remain poorly understood. This review summarizes the current knowledge of the gene regulatory network underlying the formation of the vertebrate midbrain-hindbrain boundary. We focus in particular on Fgf8 and its regulatory landscape from an evolutionary perspective.
The Spemann-Mangold organiser and the dissemination of its discovery in interwar Finland.
Neiro J
Int J Dev Biol · 2024 · PMID 40053061 · Publisher ↗
A century has passed since the publication of the discovery of the Spemann-Mangold organiser, most visibly celebrated by the Festschrift in and the conference in September 2024. In honour of the anniversary, the Fests...
A century has passed since the publication of the discovery of the Spemann-Mangold organiser, most visibly celebrated by the Festschrift in and the conference in September 2024. In honour of the anniversary, the Festschrift commemorates and reviews the history of the Spemann school of embryology and the later developments in the quest to understand the mechanistic underpinnings of the organiser. Here, I share a few new and untold insights from the Finnish archives on how the discovery of the organiser was communicated to and within Finland in the 1920s and '30s. The Finnish zoologists Alexander Luther and Gunnar Ekman had been visiting scholars in Spemann's laboratory, brought the field of experimental embryology to their home country, and incorporated it into the curriculum. Especially Ekman taught embryology to a generation of students in both tertiary and secondary education, created the Finnish terminology of the field, and actively popularised the latest discoveries in various books and journals. Intriguingly, the archives reveal that Ekman published a synopsis of the organiser experiment in Finnish in the spring of 1924 prior to the publication of the original article in September, and invited Spemann to visit Finland in September 1925. These efforts consolidated the popularity of the Spemann school of experimental embryology in Finnish academia, and shed light on "how experimental embryology was transplanted to Finland".
Developmental Biology in Nordic Countries.
Vainio S, Kuure S
Int J Dev Biol · 2024 · PMID 40053060 · Publisher ↗
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Strontium-doped hydroxyapatite and its role in osteogenesis and angiogenesis.
Ran L, Liu L, Gao J … +6 more , Pan Y, Ramalingam M, Du X, Liu Y, Cheng L, Shi Z
Int J Dev Biol · 2023 · PMID 37975329 · Publisher ↗
For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown...
For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management. The doped Sr can improve the physicochemical properties of HA and enhance its angiogenic and bone regeneration ability. Nevertheless, no study has reviewed the design strategy of Sr-doped HA (Sr-HA) to understand its biological roles. Therefore, in this article, we review recent developments in Sr-HA preparation and its effect on osteogenesis and angiogenesis and along with key suggestions for future research and development.
Evaluation of changes of apelin and apelin receptor (APJ) expression in cervix-uterus and placental axis in an LPS-induced preterm labor model.
Avci S, Golal E, Acar N
Int J Dev Biol · 2023 · PMID 37937415 · Publisher ↗
Although preterm birth is among the preventable causes of maternal and infant death, its mechanism has not yet been clarified. When evaluated in terms of the results, the psycho-social burden of mother-infant losses and...
Although preterm birth is among the preventable causes of maternal and infant death, its mechanism has not yet been clarified. When evaluated in terms of the results, the psycho-social burden of mother-infant losses and the costs of rehabilitation, care, and treatment for postpartum sequelae are high. When evaluated in terms of its causes, infection/inflammation has an important place. Therefore, it is essential to understand the role of pro- and anti-inflammatory proteins in the process. In our study, apelin and apelin receptor (APJ) expression in the cervix-uterus and placental axis were evaluated at tissue and protein levels in pregnant and non-pregnant control, sham, PBS, and LPS groups in the infection model in which LPS induction was performed by midline laparotomy, in CD-1 mice. The evaluation of this axis regarding apelin and apelin receptor in the preterm birth model is new in the literature. Apelin is expressed more intensely in uterine epithelial cells than in the cervix. In the placenta, expression is more intense in the junctional zone compared to other zones. Apelin protein levels decrease significantly in the cervix and placenta whereas it increases in the uterus. While no change was observed in the expression of the apelin receptor at the tissue and protein level in the cervix and uterus, it increased in both aspects in the placenta in the invasive procedure groups. We propose that the decrease in apelin protein due to LPS in the preterm delivery model may be related to the effort to compensate for the balance deteriorated in the pro-inflammatory direction with post-transitional modification at the tissue level. The tendency of apelin to increase with pregnancy has led to the conclusion that it is necessary for a healthy pregnancy. Although the apelin receptor does not change with inflammation, it is necessary to investigate the mechanisms associated with its stress and trauma-induced increase, since it increases in the invasive procedure group.
Insights into the role of the Wnt signaling pathway in the regeneration of animal model systems.
Walczyńska KS, Zhu L, Liang Y
Int J Dev Biol · 2023 · PMID 37937414 · Publisher ↗
Regeneration enables the regrowth and restoration of missing body parts. It is a common phenomenon among animals. However, only some species exhibit remarkable regeneration capabilities and can regenerate organs such as...
Regeneration enables the regrowth and restoration of missing body parts. It is a common phenomenon among animals. However, only some species exhibit remarkable regeneration capabilities and can regenerate organs such as limbs, lenses or hearts. Regeneration has been widely studied, thereby giving rise to new fields, such as regenerative medicine. Furthermore, regeneration has the potential to be applied to the human body. However, the molecular mechanisms governing this process should be elucidated first. Recent advancements in research methods have led to the identification of numerous signaling pathways involved in regeneration. One of them, the Wnt transduction pathway, is an ancient and evolutionarily conserved pathway that plays an important role in both embryonic development and regeneration. The Wnt pathway plays an important role during the regeneration process, as it is implicated in cell fate determination, cell migration, cell polarity and adult cell homeostasis. To date, two major Wnt pathways have been identified: the canonical (β-catenin dependent) pathway and the non-canonical pathway. The latter pathway can be further divided into planar cell polarity, the Wnt/Ca2+ pathway and the JNK pathway. In this review, we summarize the current state of knowledge regarding the Wnt signaling pathway and its role in regeneration, with a particular emphasis on key model species.
Valproic acid effects on human adipose-derived stem cell differentiation into oligodendrocytes and improved remyelination in a mouse model of Multiple Sclerosis.
Ghosouri S, Bakhtiari M, Mitra S … +1 more , Ghasemi N
Int J Dev Biol · 2023 · PMID 37937413 · Publisher ↗
Valproic acid (VPA), a neuroprotective agent and inhibitor of GSK3-β, along with human Adipose-Derived Stem Cells (hADSCs) have been proposed to be potential therapeutic agents for neurodegenerative disorders. In the pre...
Valproic acid (VPA), a neuroprotective agent and inhibitor of GSK3-β, along with human Adipose-Derived Stem Cells (hADSCs) have been proposed to be potential therapeutic agents for neurodegenerative disorders. In the present study, we have assessed the effects of VPA alone or in combination with hADSCs on oligodendrocyte differentiation, remyelination, and functional recovery in a mouse model of Multiple Sclerosis (MS). These MS-model mice were randomly divided into cuprizone, sham, VPA, hADSC, and VPA/hADSC groups, with 10 mice considered a control group (healthy mice). The hanging wire test was used to measure motor behavior. To estimate the level of myelination, we performed toluidine blue staining and immunofluorescent staining for OLIG2 and MOG-positive cells. Real-time PCR was used to evaluate the expression of β-catenin, human and mouse Mbp, Mog, and Olig2 genes. Remyelination and motor function improved in mice receiving VPA, hADSCs, and especially VPA/hADSCs compared to the Cup and Sham groups (). Additionally, the number of MOG and OLIG2 positive cells significantly increased in the VPA/hADSCs group compared to the Cup and Sham groups (). The expression of β-catenin, myelin and the other oligodendrocyte-specific genes was significantly higher in the VPA recipient groups. Valproic acid can enhance the differentiation of stem cells into oligodendrocytes, making it a potential candidate for MS treatment.
Polarized contact behavior in directionally migrating gastrula mesendoderm.
Nagel M, Winklbauer R
Int J Dev Biol · 2023 · PMID 37732810 · Publisher ↗
The control of cell-cell adhesion and detachment is essential for collective migration and cell rearrangement. Here, we have used the contact behavior of gastrula mesoderm explants migrating directionally on ectoderm co...
The control of cell-cell adhesion and detachment is essential for collective migration and cell rearrangement. Here, we have used the contact behavior of gastrula mesoderm explants migrating directionally on ectoderm conditioned substratum to study the regulation of active cell-cell detachment. When colliding laterally, explants repelled each other, whereas they fused front-to-back when aligned in the direction of migration. For this mesoderm polarization by the substratum, we identified three control modules. First, PDGF-A signaling normally suppresses contact-induced collapse of lamellipodia in a polarized manner. Disruption of PDGF-A function, or of Xwnt6, decreased the polarization of explant contact behavior. Second, the Wnt receptor Xfz7 acted upstream of the kinase Pak1 to control explant fusion independently of PDGF-A-promoted lamellipodia stability. Third, ephrinB1 acted with Dishevelled (Dvl) in front-to-back explant fusion. The second and third modules have been identified previously as regulators of tissue separation at the ectoderm-mesoderm boundary. On non-polarizing, fibronectin-coated substratum, they controlled repulsion between explants in the same way as between tissues during boundary formation. However, explant repulsion/fusion responses were reversed on conditioned substratum by the endogenous guidance cues that also control oriented contact inhibition of lamellipodia. Together, control modules and substratum-bound guidance cues combine preferential front-back adhesion and diminished lateral adhesion of cells to promote collective directional mesoderm migration.
Characterization of the developing axolotl nasal cavity supports multiple evolution of the vertebrate choana.
Chami B, Bates B, Shaheen L … +1 more , Abramyan J
Int J Dev Biol · 2023 · PMID 37548017 · Publisher ↗
All tetrapods (mammals, birds, reptiles, and amphibians) share the ability to breathe with their mouths closed due to the formation of choanae, which are openings that allow communication between the nasal and oral cavit...
All tetrapods (mammals, birds, reptiles, and amphibians) share the ability to breathe with their mouths closed due to the formation of choanae, which are openings that allow communication between the nasal and oral cavities. In most fishes, the nasal cavities serve a strictly olfactory function, possessing incurrent and excurrent nares that lie outside of the mouth and therefore, never communicate with the respiratory system. It is not until the evolution of tetrapods, in which the nasal cavities consistently open into the mouth, that they are used both for olfaction and for respiration. However, this developmental transition is poorly understood, with no consensus on the evolutionary origin of the choana in various groups despite decades of debate. Here, we use high-contrast 3D imaging in conjunction with histology and apoptotic cell analysis in non-mineralized embryonic tissues to study the formation of the choana in the axolotl (), an aquatic salamander species. We show that the axolotl choana forms from an extension of the embryonic nasal sac, which pushes through intervening mesenchyme and connects with the palate epithelium of the oral cavity, eventually breaking through. This mechanism differs from caecilians, mammals and reptiles, where fusion across a bucconasal groove plays an active role in choana formation. Nevertheless, caecilians, mammals and axolotls converge on the development of a transient epithelial tissue that has to break down in order to develop a patent choana, adding another twist to the intriguing arguments on the evolutionary history of the choana.
Conditions for transplantation of primordial germ cells in the yellowtail tetra, .
Coelho GCZ, Carvalho GB, Monzani PS … +4 more , Lopez LS, do Nascimento NF, Senhorini JA, Yasui GS
Int J Dev Biol · 2023 · PMID 37548016 · Publisher ↗
Biotechniques, including surrogate propagation derived from primordial germ cell (PGC) transplantation, are valuable tools for the reconstitution of endangered fish species. Although promising, there are no previous stud...
Biotechniques, including surrogate propagation derived from primordial germ cell (PGC) transplantation, are valuable tools for the reconstitution of endangered fish species. Although promising, there are no previous studies reporting such approaches using neotropical fish species. The aim of this study was to establish germline chimeras in neotropical fish by using the yellowtail tetra as a model species of the order Characiformes. Germline chimeras were obtained after transplantation of PGCs cultivated under different conditions: saline medium and supplemented with DMEM, amino acids, vitamins, glutamine, pyruvate, and fetal bovine serum, and subsequently transplanted into triploids and triploid hybrids from the cross between (♀) and (♂). The results indicate ectopic migration in host embryos after transplantation of PGCs cultivated in saline medium. However, PGCs cultivated in supplemented medium migrated to the region of the gonadal ridge in 4.5% of triploid and 19.3% in triploid hybrid. In addition, the higher expression of and genes was found in PGCs cultivated in supplemented culture medium. This indicates that the culture medium influences the maintenance and development of the cultivated cells. The expression levels of and (related to the differentiation and migration of PGCs) were decreased in PGCs from the supplemented culture medium, supporting the results of ectopic migration. This is the first study to report the transplantation of PGCs to obtain germline chimera in neotropical species. The establishment of micromanipulation procedures in a model neotropical species will open new insights for the conservation of endangered species.
Importance of the filamin A-Sav1 interaction in organ size control: evidence from transgenic mice.
Zhang H, Yang Z, Nakamura F
Int J Dev Biol · 2023 · PMID 37548015 · Publisher ↗
The nucleocytoplasmic translocation of yes-associated protein 1 (YAP1) controls the growth of animal tissues and organs. YAP1 binds to transcription factors in the nucleus to activate the transcription of proliferation a...
The nucleocytoplasmic translocation of yes-associated protein 1 (YAP1) controls the growth of animal tissues and organs. YAP1 binds to transcription factors in the nucleus to activate the transcription of proliferation and anti-apoptotic genes. The Hippo pathway prevents the nuclear translocation of YAP1 by phosphorylating YAP1, while mechanical forces promote it by opening the nuclear pore complex and stimulating other signaling pathways. Recently we found that Protein salvador homolog 1 (SAV1), a component of the Hippo pathway, interacts with filamin A (FLNA) in a force-dependent manner, raising a possibility that the Hippo pathway is regulated by mechanical force through the FLNA-SAV1 axis. To test this hypothesis, we generated conditional knock-in (KI) mice expressing non-Flna-binding mutant Sav1 in hepatocytes by crossing with mice carrying Cre recombinase driven by the serum albumin (alb) gene promoter. Unexpectedly, the insertion of the flox cassette skipped exon 2, resulting in a shorter Sav1 in all the transgenic mice. Since exon 2 encodes a fragment containing a Flna-binding domain, we analyzed both point mutant KI and exon 2-deleted mutant mice. Here we show that disruption of the Flna-Sav1 interaction in the mouse liver promotes apoptosis and suppresses tissue and organ growth without affecting the phosphorylation level of Yap1. These results provide evidence that the growth of animal tissues and organs is regulated by apoptosis downstream of the force-dependent FLNA-SAV1 interaction, at least in part.
The Dyslexia-associated gene is involved in neuronal migration in the developing chick visual system.
Charish J, Harada H, Chen X … +3 more , Wälchli T, Barr CL, Monnier PP
Int J Dev Biol · 2023 · PMID 37410671 · Publisher ↗
The gene KIAA0319-Like (KIAA0319L) is thought to confer susceptibility for developmental dyslexia. Dyslexia may be caused by alterations in neuronal migration, and in utero knockdown of KIAA0319L in rats indicated migrat...
The gene KIAA0319-Like (KIAA0319L) is thought to confer susceptibility for developmental dyslexia. Dyslexia may be caused by alterations in neuronal migration, and in utero knockdown of KIAA0319L in rats indicated migration errors. However, studies carried out with KIAA0319L knockout mice did not reveal an altered neuronal migration phenotype. Gene knockout may activate compensatory mechanisms to buffer against genetic mutations during development. Here we assessed the role of KIAA0319L on migrating neurons in the chick developing tectum. Whole mount in situ hybridization was performed for KIAA0319L on embryonic day (E)3 - E5 chick embryos and in situ hybridization on sections was performed at later stages. The specificity and efficiency of engineered microRNA (miRNA) constructs targeting KIAA0319L for knocking down KIAA0319L were verified. miRNAs were electroporated into E5 chick optic tecta. Our studies demonstrate that KIAA0319L is expressed in the developing chick visual system, as well as in the otic vesicles. Knockdown of KIAA0319L in the optic tectum results in abnormal neuronal migration, strengthening the argument that KIAA0319L is involved in this developmental process.
DNA methyltransferase (Dnmt) silencing causes increased Cdx2 and Nanog levels in surviving embryos.
Uysal F, Sukur G, Bozdemir N … +1 more , Cinar O
Int J Dev Biol · 2023 · PMID 37272433 · Publisher ↗
Epigenetic mechanisms are one of the essential regulators of gene expression which do not involve altering the primary nucleotide sequence. DNA methylation is considered among the most prominent epigenetic mechanisms in...
Epigenetic mechanisms are one of the essential regulators of gene expression which do not involve altering the primary nucleotide sequence. DNA methylation is considered among the most prominent epigenetic mechanisms in controlling the functions of genes related to cell differentiation, cell cycle, cell survival, autophagy, and embryo development. DNA methyl transferases (Dnmts) control DNA methylation, the levels of which are differentially altered during embryonic development, and may determine cell differentiation fate as in the case of pluripotent inner cell mass (ICM) or trophectoderm (TE). In this study, we aimed to analyze the role of Dnmt1 and Dnmt3a enzymes in ICM (using the Nanog marker) and TE (using the Cdx2 marker) differentiation, autophagy (using p62 marker), reactive oxygen species (ROS) production, and apoptosis (using TUNEL) during mouse preimplantation embryo development. Following knockdown of and in zygotes, expression levels of Cdx2 in the trophectoderm and Nanog in the inner cell mass were measured, as well as p62 levels, reactive oxygen species (ROS) production, and apoptosis levels after 96 hours in embryo culture. We found that knockdown of Dnmt1 or Dnmt3a significantly induced Cdx2 and Nanog expression. Similarly, p62 expression, ROS levels and apoptosis significantly increased after silencing. This study shows that Dnmt genes are highly crucial for embryonic fate determination and survival. Further studies are required to reveal the specific targets of these methylation processes related to cell differentiation, survival, autophagy, and ROS production in mouse and human preimplantation embryos.
Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp.
Enkhmandakh B, Bayarsaihan D
Int J Dev Biol · 2023 · PMID 37078362 · Publisher ↗
SOX transcription factors play key roles in cell differentiation and cell fate determination during development. Using single-cell RNA-sequencing data, we examined the expression profiles of genes in the mouse incisor d...
SOX transcription factors play key roles in cell differentiation and cell fate determination during development. Using single-cell RNA-sequencing data, we examined the expression profiles of genes in the mouse incisor dental pulp. Our analysis showed that , , , , and are mainly expressed in mesenchymal stem/stromal cells (MSCs) representing osteogenic cells at different stages of differentiation. We found that in several MSCs, genes co-expressed with regulatory genes such as , , , , , , and . In addition, family genes colocalized with and , which are highly enriched in MSCs undergoing osteoblast differentiation. A protein interaction network analysis uncovered that CREBBP, CEBPB, TLE1, TWIST1, and members of the HDAC and SMAD families are interacting partners of RUNX2 and LEF1 during skeletal development. Collectively, the distinct expression patterns of the SOX transcription factors suggest that they play essential regulatory roles in directing lineage-specific gene expression during differentiation of MSCs.
Circ-JA760602 promotes the apoptosis of hypoxia-induced cardiomyocytes by transcriptionally suppressing BCL2.
Li C, Wang J, Feng J … +5 more , Zhou G, Jiang Y, Luo C, Cheng Z, Li J
Int J Dev Biol · 2023 · PMID 37078361 · Publisher ↗
Acute myocardial infarction (AMI) is myocardial necrosis caused by the complete or partial obstruction of a coronary artery. Circular RNAs (circRNAs) have been proven as regulators in the progression of various human dis...
Acute myocardial infarction (AMI) is myocardial necrosis caused by the complete or partial obstruction of a coronary artery. Circular RNAs (circRNAs) have been proven as regulators in the progression of various human diseases, including AMI. However, the role of novel circ-JA760602 in AMI remains unknown. Here, we investigated the role of circ-JA760602 in modulating the apoptosis of hypoxia-induced AMI cells using the AC16 cardiomyocyte in vitro cell model. The expression of circ-JA760602 in AC16 cardiomyocytes subjected to hypoxia was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was measured by cell counting kit-8 (CCK-8) assay. Apoptosis of cardiomyocytes was evaluated by TUNEL assay and flow cytometry analysis. The cellular location of circ-JA760602 was identified through fluorescence in situ hybridization (FISH) assay and subcellular fractionation assay. The downstream molecular mechanisms of circ-JA760602 were demonstrated by luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay. Rescue assays were performed to demonstrate the effects of BCL2 knockdown on circ-JA760602 silencing-mediated cardiomyocyte apoptosis. Circ-JA760602 expression was elevated after hypoxia treatment. Knockdown of circ-JA760602 enhanced viability and curbed apoptosis of hypoxia-treated cardiomyocytes. EGR1 and E2F1 could activate BCL2 transcription. Cytoplasmic circ-JA760602 bound with EGR1 and E2F1 to thus inhibit their nuclear translocation. BCL2 knockdown reversed the effects of circ-JA760602 silencing on the apoptosis of hypoxia-treated AC16 cells. Circ-JA760602 promotes hypoxia-induced apoptosis of cardiomyocytes by binding with EGR1 and E2F1 to inhibit the transcriptional activation of BCL2.
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