Biology subjects

Larson, E. D.

Publications and source records attributed to Larson, E. D..

17 recordsLinked to original sources

bioRxiv2026

Myeloid cell reprogramming drives enhanced defense against Streptococcus pneumoniae lung infection following exposure to commensal Prevotella

Clinical data link the prevalent respiratory tract anaerobe Prevotella with reduced pneumonia mortality, but the mechanisms directing Prevotella regulation of lung immune homeostasis are unclear. Here, single-cell RNA sequencing was employed to define the transcriptional immune signatures underlying improved clearance of Streptococcus pneumoniae following lung exposure to Prevotella melaninogenica. Overall, we observed a substantial shift in myeloid cell transcriptional programming from interferon-dominant to a more antibacterial profile in S. pneumoniae-infected mice after pre-exposure to P. melaninogenica, correlating with increased macrophage and neutrophil phagocytosis of S. pneumoniae and improved pathogen clearance. In neutrophils, TNF signaling through TNFR2 was essential for increased antimicrobial function. Moreover, improved defense required CCR2-dependent monocyte-derived macrophages, with selective enrichment of more a mature Cxcl3+ population which was distinct from the hallmark S. pneumoniae-associated C1qa+ population enriched in the absence of effective clearance. Together, these findings inform the myeloid cell transcriptional changes associated with natural infection resistance mediated by pulmonary microbial exposures.

microbiology↗

bioRxiv2025

Differential usage of two, distinct DNA-binding domains regulates tissue-specific occupancy of the pioneer factor Zelda

Pioneer transcription factors act at the top of gene-regulatory networks by promoting accessible chromatin at the cis-regulatory regions that drive gene expression. Despite their ability to bind closed chromatin, pioneer factors occupy distinct binding sites in different tissues. The pioneer factor Zelda promotes the undifferentiated fate in both the early Drosophila embryo and in the neural stem cells (neuroblasts) of the larval brain. Tissue-specific binding by Zelda identifies cell-type specific enhancers, which are enriched for different DNA-sequence motifs. We investigated the features that promoted cell-type specific occupancy by testing the role of conserved, structured protein domains in the capacity of Zelda to promote the embryonic and neuroblast cell fates. We unexpectedly identified that the most deeply conserved region in Zelda, the second zinc finger, has opposing functions in the embryo and neuroblasts. We showed that this zinc finger is a previously unrecognized DNA-binding domain that is specifically required for Zelda binding to a G-rich motif in larval neuroblasts. The pioneering function of Zelda depends largely on the C-terminal cluster of zinc fingers that promotes binding in the early embryo, suggesting that pioneer function may depend on how Zelda engages the genome. As opposed to co-factor expression or chromatin environment, our data identify tissue-specific usage of two, widely separated DNA-binding domains as the mechanism controlling tissue-specific binding and activity.

developmental biology↗

bioRxiv2024

PDGFRα signaling regulates Srsf3 transcript binding to affect PI3K signaling and endosomal trafficking

Signaling through the platelet-derived growth factor receptor alpha (PDGFR) plays a critical role in craniofacial development, as mutations in PDGFRA are associated with cleft lip/palate in humans and Pdgfra mutant mouse models display varying degrees of facial clefting. Phosphatidylinositol 3-kinase (PI3K)/Akt is the primary effector of PDGFR signaling during skeletal development in the mouse. We previously demonstrated that Akt phosphorylates the RNA-binding protein serine/arginine-rich splicing factor 3 (Srsf3) downstream of PI3K-mediated PDGFR signaling in mouse embryonic palatal mesenchyme (MEPM) cells, leading to its nuclear translocation. We further showed that ablation of Srsf3 in the murine neural crest lineage results in severe midline facial clefting, due to defects in proliferation and survival of cranial neural crest cells, and widespread alternative RNA splicing (AS) changes. Here, we sought to determine the molecular mechanisms by which Srsf3 activity is regulated downstream of PDGFR signaling to control AS of transcripts necessary for craniofacial development. We demonstrated via enhanced UV-crosslinking and immunoprecipitation (eCLIP) of MEPM cells that PDGF-AA stimulation leads to preferential binding of Srsf3 to exons and loss of binding to canonical Srsf3 CA-rich motifs. Through the analysis of complementary RNA-seq data, we showed that Srsf3 activity results in the preferential inclusion of exons with increased GC content and lower intron to exon length ratio. Moreover, we found that the subset of transcripts that are bound by Srsf3 and undergo AS upon PDGFR signaling commonly encode regulators of PI3K signaling and early endosomal trafficking. Functional validation studies further confirmed that Srsf3 activity downstream of PDGFR signaling leads to retention of the receptor in early endosomes and increases in downstream PI3K-mediated Akt signaling. Taken together, our findings reveal that growth factor-mediated phosphorylation of an RNA-binding protein underlies gene expression regulation necessary for mammalian craniofacial development.

molecular biology↗

bioRxiv2023

PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation

The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with one another by binding to growth factors at the plasma membrane and activating intracellular signaling pathways to elicit responses such as migration, proliferation, survival and differentiation. The PDGFR family consists of two receptors, PDGFR and PDGFR{beta}, that dimerize to form PDGFR homodimers, PDGFR/{beta} heterodimers and PDGFR{beta} homodimers. Here, we overcame prior technical limitations in visualizing and purifying PDGFR/{beta} heterodimers by generating a cell line stably expressing C-terminal fusions of PDGFR and PDGFR{beta} with bimolecular fluorescence complementation fragments corresponding to the N-terminal and C-terminal regions of the Venus fluorescent protein, respectively. We found that these receptors heterodimerize relatively quickly in response to PDGF-BB ligand treatment, with a peak of receptor autophosphorylation following 5 minutes of ligand stimulation. Moreover, we demonstrated that PDGFR/{beta} heterodimers are rapidly internalized into early endosomes, particularly signaling endosomes, where they dwell for extended lengths of time. We showed that PDGFR/{beta} heterodimer activation does not induce downstream phosphorylation of ERK1/2 and significantly inhibits cell proliferation. Further, we characterized the PDGFR dimer-specific interactome and identified MYO1D as a novel protein that preferentially binds PDGFR/{beta} heterodimers. We demonstrated that knockdown of MYO1D leads to retention of PDGFR/{beta} heterodimers at the plasma membrane, resulting in increased phosphorylation of ERK1/2 and increased cell proliferation. Collectively, our findings impart valuable insight into the molecular mechanisms by which specificity is introduced downstream of PDGFR activation to differentially propagate signaling and generate distinct cellular responses. One-sentence summaryPDGFR/{beta} heterodimer binding to MYO1D contributes to rapid internalization of the dimerized receptors, thereby negatively affecting downstream ERK1/2 signaling and cellular proliferation.

cell biology↗

bioRxiv2022

Low-level repressive histone marks fine-tune stemness gene transcription in neural stem cells

Coordinated regulation of stemness gene activity by transcriptional and translational mechanisms poise stem cells for a timely cell-state transition during differentiation. Although important for all stemness-to-differentiation transitions, mechanistic understanding of the fine-tuning of stemness gene transcription is lacking due to the compensatory effect of translational control. We used intermediate neural progenitor (INP) identity commitment to define the mechanisms that fine-tune stemness gene transcription in fly neural stem cells (neuroblasts). We demonstrate that the transcription factor FruitlessC (FruC) binds cis-regulatory elements of most genes uniquely transcribed in neuroblasts. Loss of fruC function alone has no effect on INP commitment but drives INP dedifferentiation when translational control is reduced. FruC negatively regulates gene expression by promoting low-level enrichment of the repressive histone mark H3K27me3 in gene cis-regulatory regions. Identical to fruC loss-of-function, reducing Polycomb Repressive Complex 2 activity increases stemness gene activity. We propose low-level H3K27me3 enrichment fine-tunes stemness gene transcription in stem cells, a mechanism likely conserved from flies to humans.

developmental biology↗

bioRxiv2022

High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro.

SO_SCPLOWUMMARYC_SCPLOWTaste buds on the tongue are collections of taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice. However, SOX2 is variably expressed among CVP cells suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show highly expressing SOX2+ cells are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium, while organoids derived from low-expressing SOX2+ progenitors are composed entirely of non-taste cells. Hedgehog and WNT/{beta}-catenin are required for taste homeostasis in adult mice, but only WNT/{beta}-catenin promotes TRC differentiation in vitro and does so only in organoids derived from higher SOX2+ taste lineage-competent progenitors.

developmental biology↗

bioRxiv2022

Premature translation of the zygotic genome activator Zelda is not sufficient to precociously activate gene expression

Following fertilization, the unified germ cells rapidly transition to a totipotent embryo. Maternally deposited mRNAs encode the proteins necessary for this reprogramming as the zygotic genome remains transcriptionally quiescent during the initial stages of development. The transcription factors required to activate the zygotic genome are among these maternally deposited mRNAs and are robustly translated following fertilization. In Drosophila, the mRNA encoding Zelda, the major activator of the zygotic genome, is not translated until one hour after fertilization. Here we demonstrate that zelda translation is repressed following fertilization by the TRIM-NHL protein Brain tumor (BRAT). BRAT also regulates Zelda levels in the larval neuroblast lineage. In the embryo, BRAT-mediated translational repression is regulated by the Pan Gu (PNG) kinase, which is triggered by egg activation. The PNG kinase phosphorylates translational regulators, suggesting that PNG kinase activity alleviates translational repression of zelda by BRAT and coupling translation of zelda with that of other regulators of early embryonic development. Using the premature translation of zelda in embryos lacking BRAT activity, we showed that early translation of a zygotic genome activator is not sufficient to drive precocious gene expression. Instead, Zelda-target genes showed increased expression at the time they are normally activated. We propose that transition through early development requires the integration of multiple processes, including the slowing of the nuclear division cycle and activation of the zygotic genome. These processes are coordinately controlled by PNG kinase-mediated regulation of translation.

developmental biology↗

bioRxiv2021

Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila

During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is driven by differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network by defining cell-type-specific enhancers.

developmental biology↗

bioRxiv2021

GAD65Cre drives reporter expression in multiple taste cell types

In taste buds, Type I cells represent the majority of cells (50-60%) and primarily have a glial-like function in taste buds. However, recent studies suggest that they have additional sensory and signaling functions including amiloride-sensitive salt transduction, oxytocin modulation of taste, and substance P mediated GABA release. Nonetheless, the overall function of Type I cells in transduction and signaling remains unclear, primarily because of the lack of a reliable reporter for this cell type. GAD65 expression is specific to Type I taste cells and GAD65 has been used as a Cre driver to study Type I cells in salt taste transduction. To test the specificity of transgene-driven expression, we crossed GAD65Cre mice with floxed tdTomato and Channelrhodopsin (ChR2) lines and examined the progeny with immunochemistry, chorda tympani recording, and calcium imaging. We report that while many tdTomato+ taste cells express NTPDase2, a specific marker of Type I cells, we see expression of tdTomato in both Gustducin and SNAP25 positive taste cells. We also see ChR2 in cells just outside the fungiform taste buds. Chorda tympani recordings in the GAD65Cre/ChR2 mice show large responses to blue light, larger than any response to standard taste stimuli. Further, several isolated tdTomato positive taste cells responded to KCl depolarization with increases in intracellular calcium, indicating the presence of voltage-gated calcium channels. Taken together, these data suggest that GAD65Cre mice drive expression in multiple taste cell types and thus cannot be considered a reliable reporter of Type I cell function.

neuroscience↗

bioRxiv2020

Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling

Signaling through the platelet-derived growth factor receptor alpha (PDGFR) is critical for mammalian craniofacial development, though the mechanisms by which the activity of downstream intracellular effectors is regulated to mediate gene expression changes have not been defined. We find that the RNA-binding protein Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFR signaling in palatal mesenchyme cells, leading to its nuclear translocation. We further demonstrate that ablation of Srsf3 in the neural crest lineage leads to facial clefting due to defective cranial neural crest cell specification and survival. Finally, we show that Srsf3 regulates the alternative RNA splicing of transcripts encoding protein kinases in the facial process mesenchyme to negatively regulate PDGFR signaling. Collectively, our findings reveal that PI3K/Akt-mediated PDGFR signaling primarily modulates gene expression through alternative RNA splicing in the facial mesenchyme and identify Srsf3 as a critical regulator of craniofacial development.

developmental biology↗

bioRxiv2020

Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function.

Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth, and show SHH overexpression in vivo alters FOXA1 and FOXA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2, and show expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.

developmental biology↗

bioRxiv2020

The pioneer factor GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal- to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.

developmental biology↗

bioRxiv2020

Transcriptional profiling reveals TRPM5-expressing cells involved in viral infection in the olfactory epithelium

BackgroundUnderstanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. ResultsHerein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells. ConclusionOur study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.

neuroscience↗

bioRxiv2019

Single Cell Transcriptional Profiling of Phox2b-Expressing Geniculate Ganglion Neurons

The sense of taste is fundamental for survival as harmful substances can be discriminated and prevented from entering the body. Taste buds act as chemosensory sentinels and detect bitter, salty, sweet, sour, and umami substances and transmit signals to afferent nerve fibers. Whether a single gustatory nerve fiber selectively is responsive to a single taste modality (through taste receptor cell activation) is a point of contention in the field.. In the present study, we present a method for single cell RNA sequencing of gustatory geniculate ganglion neurons and compare the results obtained to two prior published works. Additionally, independent reanalysis of the raw data from these previous studies confirms molecular heterogeneity of ganglion neurons. Multiple gustatory clusters are found, and we compare cluster markers identified by the original works and those identified in the present study. Across all datasets and analyses, specific clusters show a high degree of correlation including a somatosensory cluster (Phox2b-, Piezo2+, Fxyd2+), a potential sweet-best cluster (Phox2b+, Spon1+, Olfm3+), and a potential sour-best cluster (Phox2b+, Penk+, Htr3a+). Additionally, a putative mechanosensitive gustatory cluster with an unknown functional role is identified (Phox2b+, Piezo2+, Calb1+). Other gustatory clusters (Phox2b+) are more varied across analyses, but are marked by Olfm3. Which, if any, clusters comprise umami-best, bitter-best, or salty-best fibers will require further study.

neuroscience↗

bioRxiv2019

A Subset of Olfactory Sensory Neurons Express Forkhead Box J1-Driven eGFP

Forkhead box protein J1 (Foxj1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. Using a Foxj1-eGFP reporter mouse, we find robust eGFP expression not only in the multi-ciliated cells of the respiratory epithelium, but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons express eGFP but these distribute throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP labeled axons terminate in many glomeruli of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons although neither receptor cell population possess motile cilia.

neuroscience↗

bioRxiv2019

Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium

Mucins are a key component of the airway surface liquid and serve many functions. Given the numerous differences in olfactory versus respiratory nasal epithelia, we hypothesized that mucins would be differentially expressed between these two areas. Secondarily, we evaluated for changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed in a mouse model to determine the expression of mucins 1, 2, 5AC and 5B in nasal respiratory and olfactory epithelia of control mice and one week after exposure to 8 gy of radiation. Mucins 1, 5AC and 5B exhibited differential expression between olfactory and respiratory epithelium while mucin 2 showed no difference. Within the olfactory epithelium, mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in respiratory epithelium it was only intermittently expressed. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the olfactory epithelium. Mucin 5B was expressed by submucosal glands in the olfactory epithelium but by surface epithelial cells in respiratory epithelium. At one-week after exposure to single-dose 8 gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine olfactory and respiratory epithelia express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 gy) does not appear to affect mucin expression at one week.\n\nAuthor RolesChristopher Kennel conceived, organized and executed the study, performed the analysis, and contributed to the manuscript.\n\nElizabeth Gould conceived and executed the study, and contributed to the manuscript.\n\nDiego Restrepo conceived and executed the study, supervised the experiments, reviewed the analysis, and contributed to the manuscript.\n\nErnesto Salcedo performed experiments and reviewed the manuscript.\n\nThad Vickery performed experiments and reviewed the manuscript.\n\nEric Larson performed experiments and reviewed the manuscript.\n\nVijay Ramakrishnan conceived and executed the study, reviewed the analysis, and contributed to the manuscript.\n\nAll authors discussed the results and implications and contributed to the final manuscript.

neuroscience↗

bioRxiv2017

A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster

In nearly all metazoans, the earliest stages of development are controlled by maternally deposited mRNAs and proteins. The zygotic genome becomes transcriptionally active hours after fertilization. Transcriptional activation during this maternal-to-zygotic transition (MZT) is tightly coordinated with the degradation of maternally provided mRNAs. In Drosophila melanogaster, the transcription factor Zelda plays an essential role in widespread activation of the zygotic genome. While Zelda expression is required both maternally and zygotically, the mechanisms by which it functions to remodel the embryonic genome and prepare the embryo for development remain unclear. Using Cas9-mediated genome editing to generate targeted mutations in the endogenous zelda locus, we determined the functional relevance of protein domains conserved amongst Zelda orthologs. We showed that neither a conserved N-terminal zinc finger nor an acidic patch were required for activity. Similarly, a previously identified splice isoform of zelda is dispensable for viability. By contrast, we identified a highly conserved zinc-finger domain that is essential for the maternal, but not zygotic functions of Zelda. Animals homozygous for mutations in this domain survived to adulthood, but embryos inheriting these loss-off-function alleles from their mothers died late in embryogenesis. These mutations did not interfere with the capacity of Zelda to activate transcription. Unexpectedly, these mutations generated a hyperactive form of the protein and enhanced Zelda-dependent gene expression. These data have defined a protein domain critical for controlling Zelda activity during the MZT, but dispensable for its roles later in development, for the first time separating the maternal and zygotic requirements for Zelda. This demonstrates that highly regulated levels of Zelda activity are exclusively required for establishing the developmental program during the MZT. We propose that tightly regulated gene expression is essential to navigate the MZT and that failure to precisely execute this developmental program leads to embryonic lethality.\n\nAUTHOR SUMMARYFollowing fertilization, the one-celled zygote must be rapidly reprogrammed to enable the development of new, unique organism. During these initial stages of development there is little or no transcription of the zygotic genome, and maternally deposited products control this process. Among the essential maternal products are mRNAs that encode transcription factors required for preparing the zygotic genome for transcriptional activation. This ensures that there is a precisely coordinated hand-off from maternal to zygotic control. In Drosophila melanogaster, the transcription factor Zelda is essential for activating the zygotic genome and coupling this activation to the degradation of the maternally deposited products. Nonetheless, the mechanism by which Zelda functions remains unclear. Here we used Cas9-mediated genome engineering to determine the functional requirements for highly conserved domains within Zelda. We identified a domain required specifically for Zeldas role in reprogramming the early embryonic genome, but not essential for its functions later in development. Surprisingly, this domain restricts the ability to Zelda to activate transcription. These data demonstrate that Zelda activity is tightly regulated, and we propose that precise regulation of both the timing and levels of genome activation is required for the embryo to successfully transition from maternal to zygotic control.

developmental biology↗