Biology subjects

Honda, S.

Publications and source records attributed to Honda, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Long-read sequencing reveals transposable element-derived chimeric transcripts at zygotic genome activation in mammalian embryos

BackgroundTransposable elements (TEs) are mobile genomic sequences that constitute one-third to one-half of the mammalian genome. Recently, TEs have been recognized for their important roles as cis-regulatory elements. TEs are broadly activated during zygotic genome activation (ZGA) in mammalian embryos, where they function as alternative promoters of host genes and drive the transcription of chimeric transcripts. However, the construction of comprehensive chimeric transcript databases based on short-read sequencing remains limited due to the repetitive and abundant nature of TEs in the genome. Here, we used long-read RNA sequencing to construct a comprehensive dataset of chimeric transcripts expressed in ZGA mouse and bovine embryos. ResultsWe identified 11,996 and 4,755 chimeric transcripts variants derived from 2,695 and 1,200 host genes in mouse and bovine, respectively, exceeding the numbers reported in previous short-read-based studies. Among them, 114 orthologous pairs produced chimeric transcripts in both species. Gene Ontology analysis revealed significant enrichment of terms related to transcriptional regulation and protein modification in mouse, whereas no terms were significantly enriched in bovine. Assessment of the protein-coding potential of the TE-driven transcripts using predicted open reading frames (ORFs) revealed that the proportion of "Protein-coding" transcripts was lower, whereas that of "LncRNA" (long non-coding RNA) was higher compared with all transcripts in both species. Among the ORFs classified as "Protein-coding", comparison with canonical ORFs revealed a tendency for the N terminus to be truncated while the C terminus remained intact in both species. TE-derived promoters used in mouse were enriched for mouse-specific TEs, whereas those in bovine were enriched for older TEs conserved among eutherians. In addition, long-read sequencing detected a greater number and proportion of TEs used as promoters in mouse and bovine than short-read sequencing. Although motif analysis identified KLF5 and OTX2 binding sites upstream of TE-derived promoters in both species, the specific TEs containing these motifs differed between the two species. ConclusionsThis study presents the first long-read sequencing analysis of chimeric transcripts in mammalian embryos in two species. Our approach revealed the functional similarities of chimeric transcripts between species, as well as species-specific differences in their TE compositions.

developmental biology↗

bioRxiv2025

Computational design of metalloproteases

Although significant progress has been made in creating de novo metalloenzymes that hydrolyze activated esters, the energetically demanding cleavage of amide bonds has remained a major challenge for enzyme design: amide bonds are significantly more stable than ester bonds, the amine leaving groups in proteins are not activated, and peptide substrates are flexible making them difficult to bind precisely. Here, we report the de novo design of zinc proteases from minimal catalytic motifs using RoseTTAFold Diffusion 2 for Molecular Interfaces, optimized for both enzyme and protein-protein interaction design. Of 135 computational designs experimentally tested, 36% had activity and cleaved precisely at the intended site. The most active design accelerates peptide bond hydrolysis by more than 10^8-fold relative to the uncatalyzed reaction, and by over 10^10-fold following the introduction of four point mutations that enhanced active-site preorganization4. Building on these capabilities, we designed metalloproteases that specifically cleave human TDP-43, the amyloid-{beta} peptide, and serum amyloid A with rate accelerations up to 9.2x10^8-fold over background. We illustrate the potential of our approach for bio-orthogonal control over cell state by generating caged cytokines and caged receptor antagonists that are selectively unmasked by our designed proteases. These results demonstrate that de novo enzyme design has advanced well beyond model reactions with activated substrates and open the door to design of proficient metallohydrolases for a wide range of applications in medicine and bioremediation.

biochemistry↗

bioRxiv2025

Pharmacological potentiation of Nav1.1 channels in interneurons mitigates tau depositions and neuronal death in a mouse model of neurodegenerative dementias

Epileptiform discharges and neuronal hyperexcitability are key pathophysiological features of Alzheimers disease and related tauopathies. We previously identified selective dynfuntion of parvalbumin-positive GABAergic interneurons (PV neurons), which regulate neural network excitability, in a tauopathy mouse model. However, the mechanistic link between PV neuron deficits, tau pathology, and neurodegeneration remains unclear. Here, we demonstrate that pharmacological enhancement of phasic PV neuron activity markedly attenuates tau accumulation and neuronal loss in a tauopathy mouse model. We developed DSR-143630, a novel activator of voltage-gated sodium channel Nav1.1, selectively expressed in PV neurons. Administration of DSR-143630 alleviated febrile seizures in Nav1.1 haploinsufficient mice and suppressed high-frequency oscillations (HFOs), an electrophysiological signature of hyperexcitability associated with cognitive impairments, in rTg4510 tau transgenic mice. Longitudinal tau PET and volumetric MRI demonstrated that DSR-143630 treatment from 4 to 11 months of age profoundly reduced age-dependent tau deposition and atrophy in the neocortex and hippocampus. Postmortem analyses further revealed decreased levels of phosphorylated tau, preservation of neuronal populations, and attenuated neuroinflammatory responses, including reactive gliosis. These findings establish PV neuron dysfunctions and consequent network hyperexcitability as key drivers of tau pathogenesis and highlight pharmacological Nav1.1 activation as a promising disease-modifying strategy for neurodegenerative tauopathies. One Sentence SummaryPharmacological potentiation of interneuronal activities attenuates aberrant network excitability, progressive tau deposition, and neurodegeneration.

neuroscience↗

bioRxiv2025

Transgenic Bax gene efficiently induces lethality in mouse early embryos

Apoptosis is an essential physiological process involved in embryonic development, immune responses, and tissue homeostasis. Despite many studies on pro-apoptotic genes, few reports have directly compared the lethality-inducing potential between them under identical conditions. In this study, we evaluated the lethality-inducing potential of three representative pro-apoptotic genes, Bax, Casp3, and Casp9, in mouse early embryos under defined conditions using the doxycycline (Dox)-inducible tetracycline-regulated gene expression system (Tet-On system) in combination with the PiggyBac transposon system. All genes were transcriptionally induced by Dox, and Bax showed the strongest lethal effect, followed by Casp9, while Casp3 did not show any effect. Notably, Bax expression severely impaired blastocyst formation and led to the intense accumulation of the DNA damage marker {gamma}H2AX. These findings suggest that introducing upstream apoptotic regulators leads to the more efficient and widespread activation of the apoptotic cascade. Additionally, an unexpected Dox-dependent increase in the expression of reverse tetracycline-controlled transactivator, which is typically driven by a constitutive promoter, was observed, raising the possibility of unanticipated regulatory mechanisms within the Tet-On system. Overall, this study is expected to contribute to a deeper understanding of apoptotic mechanisms and future advancements in regenerative medicine, reproductive engineering, and cancer research.

bioengineering↗

bioRxiv2025

Pleasure in groove is associated with neuromelanin levels in the substantia nigra of younger healthy individuals: A neuromelanin-sensitive MRI study

The pleasurable urge to move in response to music is called groove. Prior research has suggested a potential link between groove and dopamine function. However, no studies to date have directly investigated the relationship between the two. Here, we aimed to assess individual dopamine function in the substantia nigra of healthy individuals using neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a non-invasive method associated with dopamine function, and to investigate the relationship between the individual dopamine proxy index and sensitivity to the groove experience. In this study, 15 younger (< 48 years) and 16 older ([greater double equals]48 years) healthy individuals participated. Participants listened to ten musical excerpts and rated the groove experience based on "pleasure" and "wanting to move." To assess whether the groove experience is related to NM levels, type of musical excerpts, and sex, we analyzed with linear mixed-effects regression models. The results showed that higher NM levels (p = 0.032) and male sex (p = 0.034) were associated with higher pleasure ratings in the younger group. For the "urge to move" ratings, type of musical excerpts was associated with ratings in both groups (ps < 0.001), where high-groove music (Janata et al., 2012) receiving higher ratings. Taken together, these results suggest that the "pleasure" aspect of the groove experience in younger individuals was related to dopamine levels in the substantia nigra, but may not be associated with the "urge to move." Thus, pleasure and the urge to move are likely to involve distinct dopaminergic pathways and mechanisms, warranting further investigation.

neuroscience↗

bioRxiv2025

Alternatively Folded State of IgG4: Acid-Induced Compaction is Common between IgG1 and IgG4

Immunoglobulin G1 (IgG1) antibodies undergo denaturation in acidic conditions, resulting in an alternatively folded state (AFS). The AFS structure is more compact than the native state. However, the prevalence of AFS in other subclasses remains largely unexplored. This study provides evidence that humanized IgG4 can also adopt AFS structure, as demonstrated through size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS) analysis. These findings suggest that the anomalous compaction of immunoglobulins G (IgGs) is resilient to variations in sequence and structure among subclasses.

biophysics↗

bioRxiv2025

Endogenous retrovirus-driven Pcgf5 plays critical roles in zygotic genome activation and noncanonical imprinting

MERVL (murine endogenous retrovirus with leucine tRNA primer) is expressed during zygotic genome activation (ZGA) in mammalian embryos. Here, we show that the Polycomb group ring finger 5 (Pcgf5), a key component of Polycomb repressive complex 1 (PRC1), forms a chimeric transcript with MT2C_Mm, one of the long terminal repeat sequences of MERVL. Knockdown of Pcgf5 reduced developmental rates and decreased H3K27me3 and H2AK119ub1 modification during embryogenesis. In addition, not only genes expressed during ZGA but also imprinting genes were upregulated in Pcgf5 knockdown embryos. Moreover, Pcgf5 was involved in the addition of the H3K27me3 modification to the maternal Xist region. This is the first report of a MERVL-regulated transcript regulating Xist expression in mouse preimplantation embryos. Our results suggest that analysis of chimeric transcripts with MERVL will provide insight into the relationship between ZGA and noncanonical imprinting.

developmental biology↗

bioRxiv2024

Branched-chain amino acid metabolism is a crucial modulator of cellular senescence

Cellular senescence is a complex stress response that results in the permanent arrest of cell proliferation. The accumulation of senescent cells occurs during aging in living organisms, and contributes to tissue dysfunction. Although there are growing lines of evidence that various metabolic changes occur in senescent cells, the link between cellular metabolism and senescence is not yet fully understood. In this study, we demonstrate that alterations in the metabolism of branched-chain amino acids (BCAAs) play a crucial role in establishing cellular senescence. Furthermore, we identified mitochondrial BCAA transamination as a crucial step in this process. Our findings show that various types of cellular stress lead to a reduction in the expression of BCAA aminotransferase 2 (BCAT2), one of the BCAA catabolic enzymes, resulting in decreased catabolism of BCAAs and reduced synthesis of glutamate. The reduction of BCAA catabolites, together with the consequent limitation in glutathione production from glutamate, triggers cellular senescence. Furthermore, we demonstrate that a reduction in BCAT2 levels alone is sufficient to induce cellular senescence, both in cultured cells and in mice. Additionally, our results demonstrate that aging alters BCAA metabolism in both mice and humans. Our findings provide new insights into the metabolic mechanisms underlying cellular senescence, with a particular focus on the role of BCAAs.

cell biology↗

bioRxiv2024

Designing monomeric IFNγ: the significance of domain-swapped dimer structure in IFNγ immune responses

IFN{gamma} can initiate immune responses by inducing the expression of major histocompatibility complex molecules, suggesting its potential for cancer immunotherapy. However, it also has an immunosuppressive function that limits its application as a therapeutic agent. IFN{gamma} has a characteristic domain-swapped dimer structure with two of the six -helices exchanged with each other. As we hypothesized that the contrasting functions of IFN{gamma} could be attributed to its unique domain-swapped structure, we designed monomeric IFN{gamma} by transforming the domain-swapped dimer structure of wild-type IFN{gamma}. We conjectured the evolution of this domain-swapped dimer and hypothesized that the current IFN{gamma} structure emerged through shortening of the loop structure at the base of the swapped domain and the accumulation of hydrophobic amino acids at the newly generated interface during domain-swapping. We then designed and generated a stable monomeric IFN{gamma} by retracing this evolutionary process, complementing the lost loop structure with a linker and replacing the accumulated hydrophobic amino acids with hydrophilic ones. We determined that the designed variant was a monomer based on molecular size and number of epitopes and exhibited activity in cell-based assays. Notably, the monomeric IFN{gamma} showed a qualitatively similar balance between immunostimulatory and immunosuppressive gene expression as wild-type IFN{gamma}. This study demonstrates that the structural format of IFN{gamma} affects the strength of its activity rather than regulating the fate of downstream gene expression.

biochemistry↗

bioRxiv2023

Heart generation via blastocyst complementation in Mesp1/2-deficient mice

Heart transplantation is the only curative option available for patients with advanced heart failure. However, donor organ shortage and graft rejection remain critical challenges in heart transplantation. Blastocyst complementation using pluripotent stem cells (PSCs) can be used to generate organs such as the pancreas and kidneys in animal models with abnormalities in essential developmental genes. Nonetheless, whether functional adult hearts can be generated with blastocyst complementation remains unclear, and it is unknown if parenchyma, blood vessels, and stroma can be generated concomitantly from PSCs using blastocyst complementation to avoid graft rejection. Here, we show the generation of functional adult hearts in acardiac Mesp1 and Mesp2 double-knockout (Mesp1/2-DKO) mice via blastocyst complementation using mouse PSCs. Our result shows that the generated hearts were structurally and functionally normal and restored embryonic lethality in Mesp1/2-DKO mice. All four cardiovascular lineages, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, and cardiac fibroblasts, were virtually entirely derived from exogenous PSCs in the myocardium. Exogenous rat PSCs also generated rat-derived xenogeneic hearts in Mesp1/2-DKO mice via interspecies blastocyst complementation. Thus, blastocyst complementation is a viable technique for generating hearts derived from PSCs and may represent significant progress toward generating rejection-free hearts.

cell biology↗

bioRxiv2023

NSUN5 is essential for proper Hippo signaling in mouse preimplantation development

AbstractNOL1/NOP2/Sun domain family, member 5 (NSUN5) is an enzyme belonging to the 5-methylcytosine (m5C) writer family that modifies rRNA and mRNA. By re-analyzing published RNA-sequencing data, we found that Nsun5 expression was increased at the 2-cell stage during mouse preimplantation development. It has been reported that m5C regulates the stability of rRNA and mRNA. Therefore, NSUN5 may affect the expression of genes required for the development and differentiation of early mouse embryos via its role in modifying RNA. The Hippo signaling pathway has been identified as a critical regulator of the segregation of inner cell mass and trophectoderm lineages during mouse embryogenesis. According to these findings, we hypothesized that NSUN5 controls cell differentiation by regulating the expression of components of the Hippo signaling pathway in mouse early embryos. Using Nsun5-specific small interfering RNAs, we efficiently knocked down Nsun5 expression in mouse preimplantation embryos, resulting in impairments in early development, including reduced blastocyst formation, smaller size, and impaired hatching from the zona pellucida. Nsun5 depletion also led to decreased cell numbers, suggesting impaired cell proliferation. Furthermore, Nsun5 knockdown embryos exhibited reduced yes-associated protein 1 (YAP1) nuclear translocation during the morula stage, potentially affecting cell differentiation. The imbalance in pluripotent and trophectoderm lineages was evident with a significant reduction in the ratio of CDX2-positive cells to OCT4-positive cells. Nsun5 depletion impacted the Hippo signaling pathway, increasing the expression of the key genes Lats1 and Lats2 during the morula stage. Our findings underscore the essential role of Nsun5 in early embryonic development by affecting cell proliferation, YAP1 nuclear translocation, and the Hippo pathway. Understanding the roles of Nsun5 in mouse early embryos will provide insights into complex regulatory networks in development, with implications for reproductive medicine and fertility research.

developmental biology↗

bioRxiv2023

ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease

AMP-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular adenosine monophosphate (AMP) levels result in AMPK activation through the binding of AMP to the {gamma}-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. In this study, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPK{gamma}1 at Ser260/Thr262 promotes AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1-/- mice despite an increased AMP/ATP ratio. We also demonstrated that MK8722, an allosteric AMPK activator, activates AMPK in the kidneys of a CKD mouse model via a pathway that is independent of AMP sensing. MK8722 treatment significantly attenuates the deterioration of renal function in CKD and is a potential therapeutic option in CKD therapeutics.

molecular biology↗

bioRxiv2023

Diagnostic histone modification analysis of individual preimplantation embryos

BackgroundWe previously reported a modification of the CUT&Tag method (NTU-CAT) that allows genome-wide histone modification analysis in individual preimplantation embryos. In the present study, NTU-CAT was further simplified by taking advantage of the Well-of-the-Well (WOW) system, which enables the processing of multiple embryos in a shorter time with less reagent and cell loss during the procedure (WOW-CUT&Tag, WOW-CAT). ResultsWOW-CAT allowed histone modification profiling from not only a single blastocyst but also from a portion of it. WOW-CAT generated similar H3K4me3 profiles as NTU-CAT, but they were closer to the profiles produced by chromatin immunoprecipitation-sequencing, such as a valley-like trend, indicating that WOW-CAT may attenuate the bias of Tn5 transposase to cut open chromatin regions. Simultaneous WOW-CAT of two halves of single blastocysts was conducted to analyze two different histone modifications (H3K4me3 and H3K27ac) within the same embryo. Furthermore, trophectoderm cells were biopsied and subjected to WOW-CAT in anticipation of preimplantation diagnosis of histone modifications. WOW-CAT allowed the monitoring of epigenetic modifications in the main body of the embryo. For example, analysis of H3K4me3 modifications of XIST and DDX3Y in trophectoderm biopsies could be used to sex embryos in combination with quantitative PCR, but without the need for deep sequencing. ConclusionsThese results suggest the applicability of WOW-CAT for flexible epigenetic analysis of individual embryos in preimplantation epigenetic diagnosis.

genomics↗

bioRxiv2023

Analysis of histone H3K4me3 modifications in bovine placenta derived from different calf-production methods

In ruminants, overgrowth of offspring produced by in vitro fertilization (IVF) is a common problem. Abnormal epigenetic modifications caused by environmental factors during the early embryonic period are suspected as an etiology of overgrowth. In this study, we investigated the genome-wide histone H3K4me3 profiles of bovine placentae that play a pivotal role in fetal development and compared their characteristics between artificial insemination (AI)- and IVF-derived samples. Cotyledons were harvested from the placentae obtained at parturition of 5 AI- and 13 IVF-derived calves, and chromatin immunoprecipitation sequencing was performed for H3K4me3. We confirmed no significant maternal tissue contamination in the samples we used. The revealed H3K4me3 profiles reflected the general characteristics of the H3K4me3 modification, which is abundantly distributed in the promoter region of active genes. By extracting common modifications from multiple samples, the genes involved in placenta-specific biological processes could be enriched. Comparison with the H3K4me3 modifications of blastocyst samples was also effective for enriching the placenta-specific features. Principal component analysis suggested the presence of differential H3K4me3 modifications in AI- and IVF-derived samples. The genes contributing to the difference were related to the developmental biological processes. Imprinted genes such as BEGAIN, ZNF215, and DLX5 were among the extracted genes. Principal component and discriminant analyses using only male samples categorized the samples into three groups based on fetal weight and calf-production methods. To our knowledge, this is the first study to profile the genome-wide histone modifications of bovine fetal placentae and reveal their differential characteristics between different calf-production methods.

genomics↗

bioRxiv2023

MYC is essential for induction of major ZGA and subsequent preimplantation development

In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts from the embryos, begins in the S phase of the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA, but its direct association with the major ZGA has not been clarified. In this study, we found that developmental arrest occurs at the two-cell stage when mouse embryos were treated with antisense oligos targeting Myc or inhibitors specific for MYC from the one-cell stage. In order to identify when MYC inhibition affected development, we applied time-limited inhibitor treatment, and found that inhibition of MYC at the two-cell, four-cell, and morula stages had no effect on preimplantation development, whereas treatment with the inhibitor at the early two-cell stage arrested development at the two-cell stage. Furthermore, transcriptome analysis revealed that when MYC function was inhibited, genes expressed in the major ZGA phase were suppressed. These results suggest that Myc is essential for the induction of major ZGA and its subsequent development. Revealing the function of Myc in preimplantation development is expected to contribute to advances in assisted reproductive technology.

developmental biology↗

bioRxiv2022

More accurate analysis of maternal effect genes by siRNA electroporation into mouse oocytes

Maternal RNAs and proteins accumulate in mouse oocytes and control the initial stages of development. The DNA in sperm combines with protamine, which is exchanged after fertilization with maternal histones, including H3.3, but the effect of H3.3 on post-fertilization development has been unclear. In this study, we established an electroporation method to introduce H3.3 siRNA into germinal vesicle (GV)-stage oocytes without removing cumulus cells. In the traditional microinjection method, cumulus cells attached to oocytes must be removed; however, we confirmed that artificially removing cumulus cells from oocytes reduced fertilization rates, and oocytes originally free of cumulus cells had reduced developmental competence. When H3.3 siRNA was introduced at the GV stage, H3.3 was still present in the maternal pronucleus and second polar body, but not in the paternal pronucleus, resulting in embryonic lethality after fertilization. This indicates that the H3.3 protein was not incorporated into the paternal pronucleus because it was repeatedly translated and degraded in a relatively short time. On the other hand, H3.3 protein incorporated into the maternal genome in the GV stage escaped degradation and remained in the maternal pronucleus after fertilization. This new method of electroporation into GV-stage oocytes without removing cumulus cells is not skill intensive and is essential for the accurate analysis of maternal effect genes. In briefFor analysis of maternal factors contained in the oocyte, suppression of genes within the oocyte is necessary. In this paper, siRNA was introduced into oocytes by electroporation, showing that maternal mRNA was suppressed efficiently.

developmental biology↗

bioRxiv2022

Getting Smaller by Denaturation: Acid-Induced Compaction of Antibodies

Protein denaturation is a ubiquitous process that occurs both in vitro and in vivo. While the molecular understanding of the denatured structures of proteins is limited, it is commonly accepted that the loss of unique intramolecular contacts makes proteins larger. Herein, we report compaction of the immunoglobulin G1 (IgG1) protein upon acid denaturation. Small-angle X-ray scattering coupled with size exclusion chromatography revealed that IgG1 radii of gyration at pH 2 were [~]75% of those at a neutral pH. Scattering profiles showed a compact globular shape, supported by analytical ultracentrifugation. The acid denaturation of proteins with size reduction is energetically costly, and acid-induced compaction requires an attractive force for domain reorientation. Such intramolecular aggregation may be widespread in immunoglobulin proteins as non-canonical structures. Herein, we discuss the potential biological significance of these non-canonical structures of antibodies.

biophysics↗

bioRxiv2022

Chimeric PRMT6 protein produced by an endogenous retrovirus promoter regulates cell fate decision in mouse preimplantation embryos

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 (Prmt6) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of MERVL, and is translated into an elongated chimeric protein (PRMT6MT2B2) whose function differs from that of the canonical PRMT6 protein (PRMT6CAN) in mouse preimplantation embryos. Overexpression of PRMT6CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6MT2B2 increased only H2AR3me2a. In addition, overexpression of PRMT6MT2B2 in one blastomere of mouse two-cell embryos promoted cell proliferation and differentiation of the blastomere into epiblast cells at the blastocyst stage, while overexpression of PRMT6CAN repressed cell proliferation. This is the first report of the translation of a chimeric protein (PRMT6MT2B2) in mouse preimplantation embryos. Our results suggest that analyzing chimeric transcripts with MERVL will provide insight into the relationship between zygotic genome activation and subsequent intra- and extra-cellular lineage determination.

developmental biology↗