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Results for “Gene Expression Regulation, Developmental”

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PubMed2026

Spatially guided in vivo single-cell functional genomics of postnatal heart.

Understanding how spatial organization and cell-cell interactions shape gene regulatory programs is central to decoding tissue development and function. The transition at birth, marked by increased circulatory demands and rapid tissue growth, requires precise spatiotemporal coordination of cardiac maturation. In this study, we generated a high-resolution spatial and temporal atlas of the postnatal mouse heart by integrating single-nucleus RNA sequencing with image-based spatial transcriptomics. This framework revealed dynamic cellular interactions, niche-specific signaling and transcriptional programs guiding cardiomyocyte maturation. To functionally test prioritized regulators in vivo and at scale, we developed PIP-seq (probe-based indel-detectable Perturb-seq), a high-throughput platform that detects single guide RNA identity, infers gene editing and profiles transcription from fixed nuclei. Applying PIP-seq to the developing postnatal heart, we identified 21 previously uncharacterized regulators of cardiomyocyte maturation, including genes essential for sarcomere assembly, metabolic reprogramming and electrophysiological transitions. Together, our findings define how microenvironmental signals and intrinsic gene programs cooperate to guide heart maturation and establish a broadly applicable framework for functional genomics in complex tissues.

Animals↗

PubMed1992

Zfp-37, a new murine zinc finger encoding gene, is expressed in a developmentally regulated pattern in the male germ line.

To begin to examine the function in the mouse testis of genes containing the zinc finger motif, we have screened an adult mouse total testis cDNA library with probes to a conserved region of zinc fingers. We have isolated cDNAs for a new murine zinc finger encoding gene that has been designated Zfp-37. Northern blot hybridization analysis revealed Zfp-37 transcripts at high levels in the testis, the only adult tissue in which Zfp-37 expression was observed. Zfp-37 was also expressed at lower levels in the mid-gestation embryo and placenta. The major testicular transcripts are 2.3 and 2.6 kb. A 4.0 kb transcript was detected at lower levels in the testis as well as in embryo and placenta. Northern blot and in situ hybridization analysis revealed that expression of Zfp-37 was most abundant in germ cells which have completed meiosis and are undergoing the complex morphogenetic changes of spermiogenesis. The pattern of expression of Zfp-37 and the presence of the zinc finger domain suggest that Zfp-37 may have a role in regulating spermiogenesis.

Amino Acid Sequence↗

PubMed1989

A trans-acting factor required for cAMP-induced gene expression in Dictyostelium is regulated developmentally and induced by cAMP.

We have identified a nuclear activity that binds specifically to a GT-rich sequence or G-box shown previously by use of deletion analysis to be required for cAMP and for developmentally induced expression of the prestalk gene pst-cathepsin (CP2). We show that the insertion of an oligonucleotide that contains the CP2 G-box restores regulated expression whereas the insertion of oligonucleotides that contain mutations in some of the G residues does not. Moreover, the mutant oligonucleotides do not compete for binding of the factor to the wild-type sequence. The activity of the G-box binding factor (GBF) is regulated developmentally with induction of activity occurring at the time of induction of pst-cathepsin expression. In a single-cell culture, GBF activity is inducible by cAMP, and its appearance is inhibited by cycloheximide, which suggests that the factor, or a protein component required for binding of the factor, is directly induced by cAMP and may be the rate-limiting factor required for cAMP induction of pst-cathepsin expression. Models for cAMP induction of prestalk genes are described.

Base Sequence↗

PubMed2026

Molting in Pancrustacea Is Characterized by Both Deeply Conserved and Recently Evolved Gene Modules.

Arthropods such as insects and crustaceans, which together form the monophyletic group Pancrustacea, possess a rigid chitinous exoskeleton that must be periodically shed through molting to allow growth and morphological change. Although molting is a deeply conserved developmental process across Arthropoda, our understanding of its molecular mechanisms is still largely derived from insect model species. Lineage-specific innovations and losses of molting-related genes raise fundamental questions about the extent of its conservation outside noninsect arthropods. Here, we investigate the evolutionary conservation of molting gene expression across five representative pancrustacean species using publicly available transcriptomic datasets. Changes in gene expression during molting are characterized by both deeply conserved and lineage-specific gene modules. Temporal gene expression analyses reveal that these lineage-specific signatures are not uniformly distributed across the molting process: the middle transitional phase is more lineage-specific, thereby exhibiting an inverse hourglass pattern. This is likely due to life-history-specific processes, development of the cuticle, and specialized structures of the exoskeleton. Overall, this study provides evidence for both the evolutionary conservation and divergence of this key postembryonic developmental process and highlights the modular architecture of the molting program.

Animals↗

PubMed1992

Identification of a set of genes with developmentally down-regulated expression in the mouse brain.

Using a subtraction cloning approach, we have isolated a set of cDNA clones from mouse neural precursor cells whose respective mRNA levels are down-regulated during the development of mouse brain. Single stranded DNA prepared from neuronal precursor cell cDNA library in lambda Zap vector was subtracted with poly (A)+ RNA prepared from postnatal and adult mouse brain to obtain several clones which show developmental down-regulation of expression. Their patterns of expression indicate that these genes may play important roles during the embryonic development and differentiation of central nervous system.

Aging↗

PubMed2025

Dynamic allelic expression in mouse mammary glands across the adult developmental cycle.

The mammary gland, which primarily develops postnatally, undergoes significant changes during pregnancy and lactation to facilitate milk production. Through the generation and analysis of 480 transcriptomes, we provide the most detailed allelic expression map of the mammary gland, cataloguing cell-type-specific expression from ex-vivo purified cell populations over 10 developmental stages, enabling comparative analysis. The work identifies genes involved in the mammary gland cycle, parental-origin-specific and genetic background-specific expression at cellular and temporal resolution, genes associated with human lactation disorders and breast cancer. Genomic imprinting, a mechanism regulating gene expression based on parental origin, is crucial for controlling gene dosage and stem cell potential throughout development. The analysis identified 25 imprinted genes monoallelically expressed in the mammary gland, with several showing allele-specific expression in distinct cell types. No novel imprinted genes were identified and the absence of biallelically expressed imprinted genes suggests that, unlike in brain, selective absence of imprinting does not regulate gene dosage in the mammary gland. This research highlights transcriptional dynamics within mammary gland cells and identifies novel candidate genes potentially significant in the tissue during pregnancy and lactation. Overall, this comprehensive atlas represents a valuable resource for future studies on expression and transcriptional dynamics in mammary cells.

Animals↗

PubMed1990

Developmentally regulated expression of calcitonin gene-related peptide at mammalian neuromuscular junction.

Using indirect immunofluorescence techniques, we have found that calcitonin gene-related peptide-like immunoreactivity is present in the neuromuscular junctions of somatic muscles as well as in almost all motor neurons of the lumbar enlargement of 1-week-old rats. It gradually decreases in both motor neurons and motor nerve endings as the animal grows up and completely disappears from the neuromuscular junctions in adult rats, persisting only in the motor nerve endings on the intrafusal fibers. In situ hybridization experiments have shown that the down-regulation of calcitonin gene-related peptide-like immunoreactivity is strictly related to a reduction in CGRP mRNA levels in the spinal motor neurons. These results indicate that the expression of CGRP is developmentally regulated in spinal cord alpha motor neurons. They also suggest that the peptide may play an important role at the immature neuromuscular junction.

Aging↗

PubMed1989

Sequences in the visna virus long terminal repeat that control transcriptional activity and respond to viral trans-activation: involvement of AP-1 sites in basal activity and trans-activation.

Visna virus is a pathogenic lentivirus of sheep whose gene expression is developmentally regulated in cells of the monocyte-macrophage lineage. Gene expression directed by the visna virus long terminal repeat (LTR) is increased in infected cells by a virus-encoded trans-acting protein. trans-Activation is mediated in part by increases in the steady-state level of mRNA. Deletion and linker-scanner mutants were constructed to locate sequences in the LTR that regulate transcription and are responsive to viral trans-activation. The activities of these mutants were tested by using them to drive transcription of the bacterial gene for chloramphenicol acetyltransferase in transient expression assays. Three regions located between-140 and the cap site were found to be important for basal transcriptional activity, and the importance of each region was found to be dependent on the cell type. Sequences responsive to viral trans-activation were found to be the same sequences required for basal transcriptional activity. The visna virus LTR contains six sequences that are homologous to the recognition site for cellular transcriptional factor AP-1 and a single sequence homologous to the recognition site for transcriptional factor AP-4. Both of these classes of binding sites appear to be important for regulating the basal level of transcription of visna virus. The AP-1-binding site most proximal to the TATA box was found to be one target for viral trans-activation. The visna virus promoter was found to be activated by serum; this serum response has also been mapped to the AP-1-related sequences in the LTR.

Base Sequence↗

PubMed1985

Approaches to the study of somatostatin biosynthesis.

Our current knowledge of the processes regulating somatostatin biosynthesis is still scarce. Approaches used for the direct investigation of somatostatin biosynthesis in different tissues include 1) analysis of incorporation of labeled amino acids into somatostatin-like immunoreactivity (SLI), 2) cell-free translation of mRNA isolated from SLI producing tissues and 3) analysis of mRNA coding for somatostatin by cDNA blot hybridization. Amino acid incorporation into SLI has been studied in a variety of systems, including anglerfish and rat pancreas, frog retina, rat dorsal root ganglia, cerebral cortex and hypothalamus. We have studied the neuronal biosynthesis of somatostatin using monolayer cultures of neonatal rat hypothalamic cells. Following pulse labeling with [3H]phenylalanine, the cellular extracts contained material that bound specifically to an immobilized anti-somatostatin antibody. Analysis of the bound label by gel chromatography and HPLC provided evidence for the presence of labeled somatostatin-14 (S-14), somatostatin-28 (S-28) and a precursor molecule of Mr 15,000 (15 K SLI). Pulse-chase experiments demonstrated a transfer of label from 15K SLI to material corresponding to S-28 and S-14. Using cloned cDNAs complementary to somatostatin mRNA, the presence of somatostatin mRNA has been demonstrated in anglerfish pancreas and intestine, rat hypothalamus and antrum, as well as in a rat medullary thyroid carcinoma and a rat pancreatic cell line. We have recently studied the developmental regulation of somatostatin gene expression in the rat brain and stomach. Messenger RNA hybridizing specifically to a rat somatostatin cDNA probe was already clearly detectable in tissue extracts derived from brains of one week old rat fetuses. A marked increase of somatostatin mRNA occurred between day 14 and day 21 of embryonic life. By contrast, in tissue extracts derived from stomach, somatostatin mRNA remained undetectable until shortly before birth. These marked differences in the tissue specific regulation of somatostatin gene expression during ontogenesis may reflect basic differences in the developmental regulation of somatostatin gene expression in neural vs. nonneural tissues or may be related to the onset of functional activity in the organs studied.

Animals↗

PubMed1987

Developmental and immune regulation of gene expression in Hymenolepis diminuta.

Gene expression and its regulation was studied in the rat tapeworm, Hymenolepis diminuta, during strobilization. RNAs extracted from the different developmental stages of the parasite were translated in vitro in a rabbit reticulocyte lysate system. Two-dimensional patterns of the translational products were compared with the 2-dimensional patterns obtained by metabolic labelling with [35S]methionine. The results indicated a post-transcriptional regulation of gene expression during strobilization in this parasite. Gene expression and its regulation was also studied in H. diminuta obtained from 'non-permissive' hosts (mice) and immune suppressed mice and compared with the parasites of the same age obtained from 'permissive' rats hosts. The 2-dimensional patterns of the in vitro translation products, obtained by translating the RNA of different groups of parasites, were compared with the patterns of gene products obtained from parasites using [35S]methionine metabolic labelling. The results indicated a massive post-transcriptional regulation of gene expression, the latter inhibited in parasites obtained from normal mice, but not in immune suppressed mice.

Animals↗

PubMed1992

Characterization of a Xenopus oocyte factor that binds to a developmentally regulated cis-element in the TFIIIA gene.

TFIIIA mRNA expression is developmentally regulated during Xenopus oogenesis. We have identified a positive-acting cis-element in the TFIIIA gene located between -671 and -629 with respect to the mRNA initiation site, termed element 3. Element 3 contributes to the efficient transcription of the TFIIIA gene in stage III oocytes, but is inactive in the normal context of the TFIIIA gene in stage VI oocytes. A trans-acting factor, termed B3, in immature ovary extracts binds to a region within element 3 containing four repeats of the consensus nucleotide sequence 5' (T/A)GGTTACT. We discuss how the developmental regulation of B3-element 3 function could be achieved in the context of the TFIIIA gene during oogenesis.

Animals↗

PubMed2025

Studying the Role of HOX Genes in Thrombocyte Development.

In our laboratory, we study thrombopoiesis and hemostasis using zebrafish as a model organism to unravel the mechanisms of differentiation and development of thrombocytes. We have shown in our earlier work that thrombocytes are functional equivalents of platelets and have transcriptional machinery similar to megakaryocytes. We recently found evidence that hox genes play a role in their development. We used piggyback gene knockdown and thrombocyte quantification assays to understand the influence of these ancient developmental regulators on thrombopoiesis. In this chapter, we describe methods used to discover these hox genes.

Animals↗

PubMed2021

Functional impact of cancer-associated cohesin variants on gene expression and cellular identity.

Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.

Animals↗

PubMed2026

Morphological changes and transcriptomic insights into skeletal development of embryos and larvae of the sea urchin Strongylocentrotus intermedius.

To explore morphological features and molecular dynamics underlying skeletogenesis in the sea urchin Strongylocentrotus intermedius, we conducted combined morphological observation and comparative transcriptome analyses across representative embryonic and larval developmental stages. Morphological results showed that triradiate spicules first emerged at the gastrula stage. The 8-arm pluteus stage was identified as a key phase for skeletal remodeling, during which new three-radiate crystals transformed into complex stereoscopic ossicles including tube feet, spines and test plates. Transcriptomic data indicated that most differentially expressed genes (DEGs) were downregulated from the blastula to gastrula. The altered expression of basal metabolic genes and extracellular matrix genes including Colp2α and calm may be correlated with the linear mineralization of early spicules, which potentially reflects an energy adjustment pattern in developing larvae. During the transition from 6-arm to 8-arm pluteus, expression changes of calmodulin-like, Colp2α and SISin18G001660 suggest potential associations with regional calcium deposition and modifications of skeletal matrix properties. This work systematically characterizes morphological traits and transcriptional dynamics of skeletogenesis in S. intermedius. Its early spiculogenesis follows the conserved developmental pattern of echinoderms, while massive formation of stereoscopic ossicles occurs at the 8-arm pluteus stage. Stage-specific transcriptional changes across key larval skeletogenic stages are uncovered, offering transcriptomic resources for functional verification of skeletal regulatory genes.

Animals↗

PubMed1989

Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites.

Visna virus gene expression is highly restricted in monocytes but is induced by monocyte-macrophage differentiation in vivo. Deletion and linker-scanning mutants, gel shift assays, and DNase I footprinting were used to identify sequences in the visna virus long terminal repeat involved in the developmental regulation of gene expression in the U937 monocytic cell line. We found that an AP-1 and an AP-4 binding site were critical for basal activity and that the AP-1 site was required for phorbol ester-inducible gene expression. These results suggest that cellular factors that interact with AP-1 sites are involved in the developmental regulation of visna virus gene expression in macrophages.

Base Sequence↗

PubMed2026

Transcriptome sequencing provides novel insights into larval development and sexual dimorphism in the firefly Aquatica leii (Coleoptera: Lampyridae).

Fireflies are regarded as one of the most charismatic beetles due to their bioluminescence and ecological importance as bioindicators of freshwater quality. However, molecular mechanisms of larval development and sexual dimorphism in aquatic species remain poorly understood. Here, we performed multi-stage transcriptomic analysis of the aquatic firefly Aquatica leii across larval instars from L2 to L6, together with adult females and males, with three biological replicates per stage. Using time-series expression clustering, differential expression analysis, and weighted gene co-expression network analysis (WGCNA), we characterized the transcriptional dynamics of continuous larval development and the onset of sex-biased gene expression. We identified a critical transcriptional transition occurred at L5-L6, marked by downregulation of early morphogenetic genes and upregulation of juvenile hormone metabolism, oxidoreductase activity, and muscle contraction genes, indicating a shift from growth to metamorphic preparation. WGCNA identified a module strongly correlated with L6 (R = 0.97) enriched for the same functions, confirming a coordinated late-larval program. Notably, genes exhibiting sex-biased expression in adults were already expressed during late larval stages (L5 and L6), and 123 genes progressively upregulated from L2 to L6 showed enrichment in chitin biosynthesis, heart contraction, and ion transport; among these, six genes maintained high expression in adults with clear male-biased (Alei052192, Alei006658, and Alei087054) or female-biased (Alei003725, Alei096818, and Alei074026) patterns. These findings establish that transcriptional foundations for sexual dimorphism and adult tissue formation are laid during late larval stages, providing the first multi-stage transcriptomic resource for aquatic firefly conservation and breeding.

Animals↗

PubMed2024

A time-resolved single-cell roadmap of the logic driving anterior neural crest diversification from neural border to migration stages.

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial-mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.

Animals↗

PubMed1991

Developmental regulation for collagen II gene expression in transgenic mice.

In order to evaluate the involvement of the type II collagen regulatory sequences in development, we have injected a construct containing a toxin gene under the control of the rat type II collagen promoter and enhancer. The construct, pDAS10-DTA, contained the diphtheria toxin A chain gene under the control of type II collagen sequences which had been used previously to target cartilagenous tissues in transgenics. Inspection of developing fetuses at various stages of gestation revealed a high number of aborted implants as well as abnormally developing fetuses. These abnormal fetuses were of small size, had shortened and underdeveloped limbs, cleft palates, and generally resembled a phenotype similar to chondrodystrophic mice. Histological comparisons of normal and abnormal fetuses indicated a reduced amount of extracellular matrix surrounding chondrocytes, and a disorganized appearance of the tissue. These results suggest that the expression of the toxin has occurred in chondrocytes and altered the survival and development of the transgenic mice. These results also indicate that the promoter and enhancer sequences contained in the transgene controlled the developmental expression of the type II collagen gene expression.

Animals↗