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Nature Communications Nov 2023Follicular helper T (Tfh) cells are essential for the formation of high affinity antibodies after vaccination or infection. Although the signals responsible for...
Follicular helper T (Tfh) cells are essential for the formation of high affinity antibodies after vaccination or infection. Although the signals responsible for initiating Tfh differentiation from naïve T cells have been studied, the signals controlling sequential developmental stages culminating in optimal effector function are not well understood. Here we use fate mapping strategies for the cytokine IL-21 to uncover sequential developmental stages of Tfh differentiation including a progenitor-like stage, a fully developed effector stage and a post-effector Tfh stage that maintains transcriptional and epigenetic features without IL-21 production. We find that progression through these stages are controlled intrinsically by the transcription factor FoxP1 and extrinsically by follicular regulatory T cells. Through selective deletion of Tfh stages, we show that these cells control antibody dynamics during distinct stages of the germinal center reaction in response to a SARS-CoV-2 vaccine. Together, these studies demonstrate the sequential phases of Tfh development and how they promote humoral immunity.
Topics: Humans; T-Lymphocytes, Helper-Inducer; T Follicular Helper Cells; COVID-19 Vaccines; Immunity, Humoral; Germinal Center; Cell Differentiation; Transcription Factors
PubMed: 38001088
DOI: 10.1038/s41467-023-43427-4 -
Journal of Speech, Language, and... Aug 2019Purpose Current approaches to speech production aim to explain adult behavior and so make assumptions that, when taken to their logical conclusion, fail to adequately... (Review)
Review
Purpose Current approaches to speech production aim to explain adult behavior and so make assumptions that, when taken to their logical conclusion, fail to adequately account for development. This failure is problematic if adult behavior can be understood to emerge from the developmental process. This problem motivates the proposal of a developmentally sensitive theory of speech production. The working hypothesis, which structures the theory, is that feedforward representations and processes mature earlier than central feedback control processes in speech production. Method Theoretical assumptions that underpin the 2 major approaches to adult speech production are reviewed. Strengths and weaknesses are evaluated with respect to developmental patterns. A developmental approach is then pursued. The strengths of existing theories are borrowed, and the ideas are resynthesized under the working hypothesis. The speech production process is then reimagined in developmental stages, with each stage building on the previous one. Conclusion The resulting theory proposes that speech production relies on conceptually linked representations that are information-reduced holistic perceptual and motoric forms, constituting the phonological aspect of a system that is acquired with the lexicon. These forms are referred to as exemplars and schemas, respectively. When a particular exemplar and schema are activated with the selection of a particular lexical concept, their forms are used to define unique trajectories through an endogenous perceptual-motor space that guides implementation. This space is not linguistic, reflecting its origin in the prespeech period. Central feedback control over production emerges with failures in communication and the development of a self-concept.
Topics: Adult; Child; Child Language; Human Development; Humans; Models, Theoretical; Phonetics; Speech
PubMed: 31465709
DOI: 10.1044/2019_JSLHR-S-CSMC7-18-0130 -
ELife Feb 2021How genetic changes are linked to morphological novelties and developmental constraints remains elusive. Here, we investigate genetic apparatuses that distinguish fish...
How genetic changes are linked to morphological novelties and developmental constraints remains elusive. Here, we investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open-chromatin regions (OCRs). Specifically, we compared mouse forelimb buds with the pectoral fin buds of an elasmobranch, the brown-banded bamboo shark (). A transcriptomic comparison with an accurate orthology map revealed both a mass heterochrony and hourglass-shaped conservation of gene expression between fins and limbs. Furthermore, open-chromatin analysis suggested that access to conserved regulatory sequences is transiently increased during mid-stage limb development. During this stage, stage-specific and tissue-specific OCRs were also enriched. Together, early and late stages of fin/limb development are more permissive to mutations than middle stages, which may have contributed to major morphological changes during the fin-to-limb evolution. We hypothesize that the middle stages are constrained by regulatory complexity that results from dynamic and tissue-specific transcriptional controls.
Topics: Animal Fins; Animals; Biological Evolution; Embryo, Mammalian; Embryo, Nonmammalian; Extremities; Limb Buds; Mice; Phylogeny; Sharks
PubMed: 33560225
DOI: 10.7554/eLife.62865 -
Frontiers in Plant Science 2021Alternation of generations between a sporophytic and gametophytic developmental stage is a feature common to all land plants. This review will discuss the evolutionary... (Review)
Review
Alternation of generations between a sporophytic and gametophytic developmental stage is a feature common to all land plants. This review will discuss the evolutionary origins of these two developmental programs from unicellular eukaryotic progenitors establishing the ability to switch between haploid and diploid states. We will compare the various genetic factors that regulate this switch and highlight the mechanisms which are involved in maintaining the separation of sporophytic and gametophytic developmental programs. While haploid and diploid stages were morphologically similar at early evolutionary stages, largely different gametophyte and sporophyte developments prevail in land plants and finally allowed the development of pollen as the male gametes with specialized structures providing desiccation tolerance and allowing long-distance dispersal. Moreover, plant gametes can be reprogrammed to execute the sporophytic development prior to the formation of the diploid stage achieved with the fusion of gametes and thus initially maintain the haploid stage. Upon diploidization, doubled haploids can be generated which accelerate modern plant breeding as homozygous plants are obtained within one generation. Thus, knowledge of the major signaling pathways governing this dual ontogeny in land plants is not only required for basic research but also for biotechnological applications to develop novel breeding methods accelerating trait development.
PubMed: 35095963
DOI: 10.3389/fpls.2021.789789 -
Blood Jun 2022Fetal and neonatal megakaryocyte progenitors are hyperproliferative compared with adult progenitors and generate a large number of small, low-ploidy megakaryocytes....
Fetal and neonatal megakaryocyte progenitors are hyperproliferative compared with adult progenitors and generate a large number of small, low-ploidy megakaryocytes. Historically, these developmental differences have been interpreted as "immaturity." However, more recent studies have demonstrated that the small, low-ploidy fetal and neonatal megakaryocytes have all the characteristics of adult polyploid megakaryocytes, including the presence of granules, a well-developed demarcation membrane system, and proplatelet formation. Thus, rather than immaturity, the features of fetal and neonatal megakaryopoiesis reflect a developmentally unique uncoupling of proliferation, polyploidization, and cytoplasmic maturation, which allows fetuses and neonates to populate their rapidly expanding bone marrow and blood volume. At the molecular level, the features of fetal and neonatal megakaryopoiesis are the result of a complex interplay of developmentally regulated pathways and environmental signals from the different hematopoietic niches. Over the past few years, studies have challenged traditional paradigms about the origin of the megakaryocyte lineage in both fetal and adult life, and the application of single-cell RNA sequencing has led to a better characterization of embryonic, fetal, and adult megakaryocytes. In particular, a growing body of data suggests that at all stages of development, the various functions of megakaryocytes are not fulfilled by the megakaryocyte population as a whole, but rather by distinct megakaryocyte subpopulations with dedicated roles. Finally, recent studies have provided novel insights into the mechanisms underlying developmental disorders of megakaryopoiesis, which either uniquely affect fetuses and neonates or have different clinical presentations in neonatal compared with adult life.
Topics: Adult; Bone Marrow; Fetus; Humans; Infant, Newborn; Megakaryocyte Progenitor Cells; Megakaryocytes; Thrombopoiesis
PubMed: 35108353
DOI: 10.1182/blood.2020009301 -
Methods in Molecular Biology (Clifton,... 2020Transgenic technologies belong to important tools of reverse genetics and biotechnology in plants. Targeted genetic modifications can reveal functions of genes of... (Review)
Review
Transgenic technologies belong to important tools of reverse genetics and biotechnology in plants. Targeted genetic modifications can reveal functions of genes of interest, change metabolic and regulatory pathways, or result in accumulation of valuable proteins or metabolites. However, to be efficient in targeted genetic modification, the chimeric gene construct should be designed properly. In particular, the promoters used to control transgene expression need to be carefully chosen. Most promoters in widely used vectors belong to strong and constitutively expressed variants. However, in many cases transgene expression has to be restricted to certain tissue, stage of development, or response to some internal or external stimuli. In turn, a large variety of tissue-specific promoters have been studied and information on their characteristics may be recovered from the literature. An appropriate promoter may be selected and used in genetic construct to optimize the transgene transcription pattern. We have previously designed the TGP database (TransGene Promoters, http://wwwmgs.bionet.nsc.ru/mgs/dbases/tgp/home.html ) collecting information from the publications in this field. Here we review the wide range of noncanonical tissue-specific and developmentally regulated promoters that might be used for transgene expression control.
Topics: Flowers; Fruit; Gene Expression Regulation, Developmental; Organ Specificity; Promoter Regions, Genetic; Seeds
PubMed: 32277449
DOI: 10.1007/978-1-0716-0356-7_4 -
Current Protocols Oct 2023The rapid succession of events during development poses an inherent challenge to achieve precise synchronization required for rigorous, quantitative phenotypic and...
The rapid succession of events during development poses an inherent challenge to achieve precise synchronization required for rigorous, quantitative phenotypic and genotypic analyses in multicellular model organisms. Drosophila melanogaster is an indispensable model for studying the development and function of higher order organisms due to extensive genome homology, tractability, and its relatively short lifespan. Presently, nine Nobel prizes serve as a testament to the utility of this elegant model system. Ongoing advancements in genetic and molecular tools allow for the underlying mechanisms of human disease to be investigated in Drosophila. However, the absence of a method to precisely age-match tissues during larval development prevents further capitalization of this powerful model organism. Drosophila spends nearly half of its life cycle progressing through three morphologically distinct larval instar stages, during which the imaginal discs, precursors of mature adult external structures (e.g., eyes, legs, wings), grow and develop distinct cell fates. Other tissues, such as the central nervous system, undergo massive morphological changes during larval development. While these three larval stages and subsequent pupal stages have historically been identified based on the number of hours post egg-laying under standard laboratory conditions, a reproducible, efficient, and inexpensive method is required to accurately age-match larvae within the third instar. The third instar stage is of particular interest, as this developmental stage spans a 48-hr window during which larval tissues switch from proliferative to differentiation programs. Moreover, some genetic manipulations can lead to developmental delays, further compounding the need for precise age-matching between control and experimental samples. This article provides a protocol optimized for synchronous staging of Drosophila third instar larvae by colorimetric characterization and is useful for age-matching a variety of tissues for numerous downstream applications. We also provide a brief discussion of the technical challenges associated with successful application of this protocol. © 2023 Wiley Periodicals LLC. Basic Protocol: Synchronization of third instar Drosophila larvae.
Topics: Animals; Humans; Drosophila; Drosophila melanogaster; Larva; Colorimetry; Pupa
PubMed: 37861353
DOI: 10.1002/cpz1.924 -
Trauma, Violence & Abuse Jul 2021Resilience following childhood maltreatment has received substantial empirical attention, with the number of studies on this construct growing exponentially in the past... (Review)
Review
Resilience following childhood maltreatment has received substantial empirical attention, with the number of studies on this construct growing exponentially in the past decade. While there is ample interest, inconsistencies remain about how to conceptualize and assess resilience. Further, there is a lack of consensus on how developmental stage influences resilience and how protective factors affect its expression. The current systematic review uses a developmental lens to synthesize findings on resilience following child maltreatment. Specifically, this article consolidates the body of empirical literature in a developmentally oriented review, with the intention of inclusively assessing three key areas-the conceptualization of resilience, assessment of resilience, and factors associated with resilience in maltreatment research. A total of 67 peer-reviewed, quantitative empirical articles that examined child maltreatment and resilience were included in this review. Results indicate that some inconsistencies in the literature may be addressed by utilizing a developmental lens and considering the individual's life stage when selecting a definition of resilience and associated measurement tool. The findings also support developmental variations in factors associated with resilience, with different individual, relational, and community protective factors emerging based on life stage. Implications for practice, policy, and research are incorporated throughout this review.
Topics: Child; Child Abuse; Humans; Resilience, Psychological
PubMed: 31405362
DOI: 10.1177/1524838019869094 -
Platelets Aug 2020A growing body of research has made it increasingly clear that there are substantial biological differences between fetal/neonatal and adult megakaryopoiesis. Over the... (Review)
Review
A growing body of research has made it increasingly clear that there are substantial biological differences between fetal/neonatal and adult megakaryopoiesis. Over the last decade, studies revealed a developmentally unique uncoupling of proliferation, polyploidization, and cytoplasmic maturation in neonatal MKs that results in the production of large numbers of small, low ploidy, but mature MKs during this period of development, and identified substantial molecular differences between fetal/neonatal and adult MKs. This review will summarize our current knowledge on the developmental differences between fetal/neonatal and adult MKs, and recent advances in our understanding of the underlying molecular mechanisms, including newly described developmentally regulated pathways and miRNAs. We will also discuss the implications of these findings on the ways MKs interact with the environment, the response of neonates to thrombocytopenia, the pathogenesis of Down syndrome-transient myeloproliferative disorder (TMD), and the developmental stage specific-manifestations of congenital amegakaryocytic thrombocytopenia.
Topics: Animals; Cell Differentiation; Gene Expression Regulation, Neoplastic; Humans; Mice; Thrombopoiesis
PubMed: 32200697
DOI: 10.1080/09537104.2020.1742879 -
Plants (Basel, Switzerland) Jun 2022A growing leaf can be divided into three sections: division zone, elongation zone, and maturation zone. In previous studies, low nitrogen (LN) inhibited maize growth and...
A growing leaf can be divided into three sections: division zone, elongation zone, and maturation zone. In previous studies, low nitrogen (LN) inhibited maize growth and development, especially leaf growth; however, the gene expression in response to LN in different regions in leaf were not clear. Here, using hydroponics and a transcriptome approach, we systematically analyzed the molecular responses of those zones and differentially expressed genes (DEG) in response to LN supply. Developmental stage-specific genes (SGs) were highly stage-specific and involved in distinct biological processes. SGs from division (SGs-DZ) and elongation zones (SGs-EZ) were more related to developmentally dependent processes, whereas SGs of the maturation zone (SGs-MZ) were more related to metabolic processes. The common genes (CGs) were overrepresented in carbon and N metabolism, suggesting that rebalancing carbon and N metabolism in maize leaves under LN condition was independent of developmental stage. Coexpression modules (CMs) were also constructed in our experiment and a total of eight CMs were detected. Most of SGs-DZ and SGs-EZ were classified into a set termed CM turquoise, which was mainly enriched in ribosome and DNA replication, whereas several genes from SGs-MZ and CGs were clustered into CM blue, which mainly focused on photosynthesis and carbon metabolism. Finally, a comprehensive coexpression network was extracted from CM blue, and several maize () genes seemed to participate in regulating photosynthesis in maize leaves under LN condition in a developmental stage-specific manner. With this study, we uncovered the LN-responsive CGs and SGs that are important for promoting plant growth and development under insufficient nitrogen supply.
PubMed: 35736701
DOI: 10.3390/plants11121550