Developmental Dynamics Research Articles

Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment.

The thymic stroma is composed of epithelial and nonepithelial cells providing separate microenvironments controlling homing, differentiation, and selection of hematopoietic precursor cells to functional T cells. Here, we explore at single-cell resolution the complex composition and dynamic changes of the nonepithelial stromal compartment across different developmental stages in the human and mouse thymus, and in an experimental model of the DiGeorge syndrome, the most common form of human thymic hypoplasia. The detected gene expression signatures identify previously unknown stromal subtypes and relate their individual molecular profiles to separate differentiation trajectories and functions, revealing an unprecedented heterogeneity of different cell types that emerge at discrete developmental stages and vary in their expression of key regulatory signaling circuits and extracellular matrix components. Together, these findings highlight the dynamic complexity of the nonepithelial thymus stroma and link this to separate instructive roles essential for normal thymus organogenesis and tissue maintenance.

Deconstructing human peri-implantation embryogenesis based on embryos and embryoids

The peri-implantation period from blastula to gastrula is one of the crucial stages of human embryo and stem cell development. During development, human embryos undergo many crucial events, such as embryonic lineage differentiation and development, structural self-assembly, pluripotency state transition, cell communication between lineages, and crosstalk between the embryo and uterus. Abnormalities in these developmental events will result in implantation failure or pregnancy loss. However, because of ethical and technical limits, the developmental dynamics of human peri-implantation embryos and the underlying mechanisms of abnormal development remain in a "black box." In this review, we summarize recent progress made toward our understanding of human peri-implantation embryogenesis based on extended in vitro cultured embryos and stem cell-based embryoids. These findings lay an important foundation for understanding early life, promoting research into human stem cells and their application, and preventing and treating infertility. We also propose key scientific issues regarding peri-implantation embryogenesis and provide an outlook on future study directions. Finally, we sum up China's contribution to the field and future opportunities.

Developmental mRNA m5C landscape and regulatory innovations of massive m5C modification of maternal mRNAs in animals

m5C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m5C maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using Drosophila as a model, we reveal that embryos lacking maternal mRNA m5C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m5C. From invertebrates to the lineage leading to humans, two waves of m5C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m5C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m5C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m5C in biology and disease.

Postnatal growth of the lumbosacral spinal segments in cat: Their lengths and positions in relation to vertebrae.

Cat is a prominent model for investigating neural networks of the lumbosacral spinal cord that control locomotor and visceral activity. We previously proposed an integral function, establishing the topographical relationship between the spinal cord segments and vertebrae in adult animals. Here, we investigated the dynamic of this topographical relationship through early and middle periods of development in kittens. We calculated the length of each vertebra relative to the total length of the region from 13th thoracic (T) to the 7th lumbar (L) vertebrae (V) as well as the length of each segment relative to the total region from T13 to the three-dimensional sacral (S) segment. As in our previous work, the length and position of VL2 were used to establish relationships between the characteristics of the segments and vertebrae. Cubic regression reliably approximates the lengths of segments relative to VL2 length. As the cat aged, the relative length of VT13 and VL1 decreased while the relative length of VL5 increased. The relative length of the T13 and L3 segments increased while the relative length of the S1-S2 segments decreased. The T13-L2 segments are descended monotonically relative to the VL1-VL2 border. The L3-S1 segments are also descended, though with more complex dynamics. The positions of the S2-S3 segments remained unchanged. To conclude, different spinal segments displayed different developmental dynamics. The revealed relationship between vertebrae and lumbosacral spinal segments may be helpful for clearly defining stimulation regions to invoke particular functions, both in experimental studies on the spinal cord and clinical treatment.

Developmental dynamics and genomic programming of GC-derived precursors that give rise to long lived plasma cells

Abstract Plasma cell (PC) precursors are generated during a germinal center (GC) response and migrate to the bone marrow (BM) where they undergo terminal differentiation into short-lived (SL) or long-lived (LL) antibody secreting cells. The developmental dynamics and genomic states of PC precursors remain to be elucidated1. We utilize a novel experimental system, involving CD138+ splenocytes isolated from NP-KLH immunized C57Bl/6J mice (21–42 dpi) and their adoptive transfer into B cell deficient mMT mice, to analyze developmental dynamics of antigen-specific PC precursors and their progeny at single-cell resolution. We demonstrate that SLPC precursors are generated earlier (d21), whilst LLPC precursors are generated later (d35) during a GC response. scRNA-seq analyses reveals increased frequency of a novel cluster of transitional cells expressing both B-lineage and plasma cell-specific genes. Coupled analyses using BCR-seq shows that NP-specific transitional cells express cell cycle genes and undergo greater clonal expansion on d35 to give rise to proliferating and quiescent PCs. Antigen-specific clonal tracking in the spleen and BM compartments suggests that the transitional cells emanating from the GC, differentiate into proliferating PCs before migrating to the BM. CITE-seq analyses and reconstitution experiments demonstrate that proliferating PCs are contained within the B220− CD138+ CD44+ CD11a+ subset and are enriched for BMPC precursors. These results reveal novel GC-derived transitional cells that generate precursors of both SLPCs and LLPCs with differing developmental and proliferation dynamics in a humoral immune response.

HSC-independent definitive lymphopoiesis persists into adult life

Abstract The stem cell theory that all blood cells are derived from hematopoietic stem cell (HSC) is a central dogma in hematology. However, exceptions are the fetal hematopoiesis in which primitive and definitive type of erythromyeloid cells are already produced from hemogenic endothelial cells (HECs) before the first HSC emergence in the mouse embryo. This early blood cell production prior to HSC emergence is called HSC-independent hematopoiesis and considered to be transient during fetus. Recent lineage-tracing studies revealed that some tissue-resident innate immune cells (e.g. brain microglia, mast cells, and certain types of γδT cells) are also produced independently of HSCs from early extra-embryonic yolk-sac (YS). Definitive T&B-lymphoid potential and multi-potent progenitor (MPP) potential have been detected in the YS and/or embryos in in vitro studies, however, the physiological presence of these cells in the embryo at pre-HSC stage remains unknown. In addition, whether HSCs in the fetal liver are the main source of innate-like B-1a cells has been controversial. Here, using complementary lineage tracing mouse models, we show that HSC-independent MPPs and HSC-independent adoptive T & B-lymphocytes persist into adult life and are gradually replaced by HSC-derived cells. Furthermore, we found that HSCs minimally contribute to the peritoneal B-1a cells, and most B-1a cells are originated directly from ECs in the YS and embryo and HSC-independent for life. Our discovery of extensive HSC-independent MPP and adoptive lymphocytes in adults attests to the complex blood developmental dynamics through embryo to adult that underpin the immune system and challenges the paradigm of HSC theory in hematology. Supported by grant from NIH R01AI121197.

Developmental dynamics of sex reprogramming by high incubation temperatures in a dragon lizard

BackgroundIn some vertebrate species, gene-environment interactions can determine sex, driving bipotential gonads to differentiate into either ovaries or testes. In the central bearded dragon (Pogona vitticeps), the genetic influence of sex chromosomes (ZZ/ZW) can be overridden by high incubation temperatures, causing ZZ male to female sex reversal. Previous research showed ovotestes, a rare gonadal phenotype with traits of both sexes, develop during sex reversal, leading to the hypothesis that sex reversal relies on high temperature feminisation to outcompete the male genetic cue. To test this, we conducted temperature switching experiments at key developmental stages, and analysed the effect on gonadal phenotypes using histology and transcriptomics.ResultsWe found sexual fate is more strongly influenced by the ZZ genotype than temperature. Any exposure to low temperatures (28 °C) caused testes differentiation, whereas sex reversal required longer exposure to high temperatures. We revealed ovotestes exist along a spectrum of femaleness to male-ness at the transcriptional level. We found inter-individual variation in gene expression changes following temperature switches, suggesting both genetic sensitivity to, and the timing and duration of the temperature cue influences sex reversal.ConclusionsThese findings bring new insights to the mechanisms underlying sex reversal, improving our understanding of thermosensitive sex systems in vertebrates.

On Becoming an Emerging Adult Parent in South Africa: Processes of Commitment, Exploration and Reconsideration of a Parental Identity

This study aimed to explore perceptions and experiences of parental identity development, with a specific focus on how the developmental dynamics of emerging adulthood intersect with processes of commitment, exploration and reconsideration of the parental role. Twenty-four South-African emerging adult parents were interviewed. Thematic analysis revealed that the intersection of the transitions towards parenthood and adulthood culminates in a nuanced expression of parental roles in relation to the themes of possibility, instability, in-betweenness, self-focus and identity exploration. Heterogeneity was seen in the expression of mixed emotions of hope and excitement about parenthood together with insecurity and struggles in the attempt to balance multiple roles, especially when facing challenges related to the South-African context. Participants prioritised responsibility and commitment to the parental role, facilitated by the support from parents, extended families and cultural norms. This research presents first steps towards a qualitative inquiry into the three-dimensional conceptualisation of parental identity formation.

Walnut N-Acetylserotonin Methyltransferase Gene Family Genome-Wide Identification and Diverse Functions Characterization During Flower Bud Development.

Melatonin widely mediates multiple developmental dynamics in plants as a vital growth stimulator, stress protector, and developmental regulator. N-acetylserotonin methyltransferase (ASMT) is the key enzyme that catalyzes the final step of melatonin biosynthesis in plants and plays an essential role in the plant melatonin regulatory network. Studies of ASMT have contributed to understanding the mechanism of melatonin biosynthesis in plants. However, AMST gene is currently uncharacterized in most plants. In this study, we characterized the JrASMT gene family using bioinformatics in a melatonin-rich plant, walnut. Phylogenetic, gene structure, conserved motifs, promoter elements, interacting proteins and miRNA analyses were also performed. The expansion and differentiation of the ASMT family occurred before the onset of the plant terrestrialization. ASMT genes were more differentiated in dicotyledonous plants. Forty-six ASMT genes were distributed in clusters on 10 chromosomes of walnut. Four JrASMT genes had homologous relationships both within walnut and between species. Cis-regulatory elements showed that JrASMT was mainly induced by light and hormones, and targeted cleavage of miRNA172 and miR399 may be an important pathway to suppress JrASMT expression. Transcriptome data showed that 13 JrASMT were differentially expressed at different periods of walnut bud development. WGCNA showed that JrASMT1/10/13/23 were coexpressed with genes regulating cell fate and epigenetic modifications during early physiological differentiation of walnut female flower buds. JrASMT12/28/37/40 were highly expressed during morphological differentiation of flower buds, associated with altered stress capacity of walnut flower buds, and predicted to be involved in the regulatory network of abscisic acid, salicylic acid, and cytokinin in walnut. The qRT-PCR validated the results of differential expression analysis and further provided three JrASMT genes with different expression profiles in walnut flower bud development. Our study explored the evolutionary relationships of the plant ASMT gene family and the functional characteristics of walnut JrASMT. It provides a valuable perspective for further understanding the complex melatonin mechanisms in plant developmental regulation.

First person – Momoe Nakajo

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Momoe Nakajo is first author on ‘ Centrosome maturation requires phosphorylation-mediated sequential domain interactions of SPD-5’, published in JCS. Momoe is a PhD student in the lab of Asako Sugimoto at the Laboratory of Developmental Dynamics, Tohoku University, Sendai, Japan, investigating the mechanisms involved in formation of microtubule-organizing centers.

Brown adipose tissue involution associated with progressive restriction in progenitor competence.

Human brown adipose tissue (BAT) undergoes progressive involution. This involution process is not recapitulated in rodents, and the underlying mechanisms are poorly understood. Here we show that the interscapular BAT (iBAT) of rabbits whitens rapidly during early adulthood. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied by loss of brown adipogenic competence of progenitors. Single-cell RNA sequencing reveals that rabbit and human iBAT progenitors highly express the FSTL1 gene. When iBAT involutes in rabbits, adipocyte progenitors reduce FSTL1 expression and are refractory to brown adipogenic recruitment. Conversely, FSTL1 is constitutively expressed in mouse iBAT to sustain WNT signaling and prevent involution. Progenitor incompetence and iBAT paucity can be induced in mice by genetic deletion of the Fstl1 gene or ablation of Fstl1+ progenitors. Our results highlight the hierarchy and dynamics of the BAT progenitor compartment and implicate the functional incompetence of FSTL1-expressing progenitors in BAT involution.

The Assessment of Dual-Cycle Identity Models Among Secondary School Students: The Hungarian Adaptation of DIDS and U-MICS.

The aim of the present study was to evaluate the factor structure and validity of the Hungarian versions of the Dimensions for Identity Development Scale (DIDS) and Utrecht-Management of Identity Commitments Scale (U-MICS). Both models assume that the iterative process of exploring and evolving commitments occurs in two distinct cycles. The sample for testing the factor structure of DIDS consisted of 808 adolescents (357 boys and 451 girls) aged between 14 and 21 years (Mage = 16.86; SD = 1.35). The sample for testing the factor structure of U-MICS consisted of 803 adolescents (353 boys and 450 girls) aged between 14 and 21 years (Mage = 16.88; SD = 1.34). Results indicated a five factor model of DIDS in the present sample. All the five dimensions correlated as hypothesized both internally and externally. In line with previous research, six clusters emerged based on the dimensions of DIDS, including ruminative moratorium. Regarding U-MICS, results indicated a three factor model in the present sample. All the three dimensions were internally and externally correlated as hypothesized regarding both ideological and interpersonal identity domains. With regard to the identity status cluster solution, five clusters emerged in both the educational and friendship domains. We found specific variation regarding identity clusters in the two identity domains. Our results support the use of these two measurements in Hungarian context. Further, our results confirm the divergent developmental dynamics of ideological and interpersonal identity domains.

Variation of floret development and grain setting characteristics in winter wheat responses to delayed sowing.

Wheat floret development has been a focus of research due to a desire to improve spike fertility, which majorly influences grain yield. Sowing date plays a vital role on grain yield in wheat, and increase in the grain number per spike of winter wheat (Triticum aestivum L.) has been obtained by delayed sowing. During the 2014-2015 and 2015-2016 growing seasons, variation in these developmental patterns was explored involving two winter wheat cultivars (Jimai 22 and Tainong 18) and five sowing dates (24 September; 1, 8, 15 and 22 October). We noticed clear differences in the grain number per spikelet; delayed sowing had a greater impact on the number of fertile florets at anthesis than grain set. Significant differences in the developmental patterns of florets among spikelet positions corresponded to variations in the floret developmental rate, with faster floret development associated with higher floret fertility. Delayed sowing did not affect the grain number near the rachis, but significantly promoted grain set on distal florets. Increased spike dry weight (SDW) did not compensate for floret size or grain weight, mainly due to enhanced assimilate partitioning to florets. Delayed sowing significantly affects floret developmental dynamics, causing differences in winter wheat floret fertility. An increased SDW concomitant with improved intra-spike partitioning before anthesis contributes to increase the distal floret numbers per spike and then optimize winter wheat spike fertility. © 2022 Society of Chemical Industry.

Identification of novel regulators required for early development of vein pattern in the cotyledons by single-cell RNA-sequencing.

SUMMARYThe leaf veins of higher plants contain a highly specialized vascular system comprised of xylem and phloem cells that transport water, organic compounds and mineral nutrients. The development of the vascular system is controlled by phytohormones that interact with complex transcriptional regulatory networks. Before the emergence of true leaves, the cotyledons of young seedlings perform photosynthesis that provides energy for the sustainable growth and survival of seedlings. However, the mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood, in part due to the complex cellular composition of this tissue. To better understand the development of leaf veins, we analyzed 14 117 single cells from 3‐day‐old cotyledons using single‐cell RNA sequencing. Based on gene expression patterns, we identified 10 clusters of cells and traced their developmental trajectories. We discovered multiple new marker genes and developmental features of leaf veins. The transcription factor networks of some cell types indicated potential roles of CYCLING DOF FACTOR 5 (CDF5) and REPRESSOR OF GA (RGA) in the early development and function of the leaf veins in cotyledons. These new findings lay a foundation for understanding the early developmental dynamics of cotyledon veins. The mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood. In this study, we comprehensively characterized the early differentiation and development of leaf veins in 3‐day‐old cotyledons based on single‐cell transcriptome analysis. We identified the cell types and novel marker genes of leaf veins and characterized the novel regulators of leaf vein.

A Thermodynamic Model for Water Activity and Redox Potential in Evolution and Development.

Reactions involving water and oxygen are basic features of geological and biological processes. To understand how life interacts with its environment requires monitoring interactions with [Formula: see text] and [Formula: see text] not only at timescales relevant to organismal growth but also over billions of years of geobiological evolution. Chemical transformations intrinsic to evolution and development were characterized by analyzing data from recent phylostratigraphic and proteomic studies. This two-stage analysis involves obtaining chemical metrics (carbon oxidation state and stoichiometric hydration state) from the elemental compositions of proteins followed by modeling the relative stabilities of target proteins against a proteomic background to infer thermodynamic parameters [oxygen fugacity, water activity, and virtual redox potential (Eh)]. The main results of this study are a rise in carbon oxidation state of proteins spanning the time of the Great Oxidation Event, a rise in virtual redox potential that coincides with the likely emergence of aerobic metabolism, and a rise in carbon oxidation state of proteins inferred from the transcriptome in late stages of Bacillus subtilis biofilm growth. Furthermore, stoichiometric hydration state of expressed proteins decreases through stages of biofilm development, drops at the same time as a drop in organismal water content during fruit fly development, and is lower for proteins with more recent gene ages, all of which support the inference of higher hydration potentials at earlier time points. These results show how the evolutionary and developmental dynamics of major chemical variables can be deciphered through thermodynamic analysis of proteins as chemical entities.

Possible Persons: Dickensian Character, Violent Play

AbstractThis essay proposes a new way of thinking about Dickens's “little” characters in The Old Curiosity Shop and Our Mutual Friend, referencing Melanie Klein's “play-technique.” Klein was the first to theorize the anxious aggressive child and to posit a complex object relating in which the damage and repair of toys mediated and modulated the unmanageability of infantile emotion. Dickensian characterization, often criticized as object-like and lacking complex interiority, can be understood to intuit the developmental dynamics that Klein would locate in interactions between the child and the thing. Dickens's increasingly interiorized protagonists are surrounded and mirrored by toylike figures that problematize the thesis of novelistic maturation, proving as essential to the depiction of a complex psychology as internal monologue or achieved Bildung.

Global DNA methylation and chondrogenesis of rat limb buds in a three-dimensional organ culture system.

Although DNA methylation epigenetically regulates development, data on global DNA methylation during the development of limb buds (LBs) are scarce. We aimed to investigate the global DNA methylation developmental dynamics in rat LBs cultivated in a serum supplemented (SS) and in chemically defined serum- and protein-free (SF) three-dimensional organ culture. Fischer rat front- and hind-LBs at the 13th and 14th gestation days (GDs) were cultivated at the air-liquid interface in Eagle’s Minimal Essential Medium (MEM) or MEM with 50% rat serum for 14 days, as SF and SS conditions, respectively. The methylation of repetitive DNA sequences (short interspersed DNA repetitive element [SINE] rat ID elements) was assessed by pyrosequencing. Development was evaluated by light microscopy and extracellular matrix glycosaminoglycans staining by safranin O. On isolation, weak safranin O staining was present only in more developed GD14 front-LBs. Chondrogenesis proceeded well in all cultures toward day 14, except in the SF-cultivated GD13 hind-LBs, where safranin O staining was almost absent on day 3 that was associated with a higher percentage of DNA methylation than in SF-cultivated GD13 front-LBs on day 3. In SF-cultivated front-LBs, a significant methylation increase between the 3rd and 14th days was detected. In SS-cultivated GD13 front-LBs, methylation increased significantly on day 3 and then decreased. In older GD14 SS-cultivated LBs, there was no increase of DNA methylation, but they were significantly hypomethylated relative to the SS-cultivated GD13 at days 3 and 14. We confirmed that the global DNA methylation increase is associated with less developed limb organ primordia that strive toward differentiation in vitro, which is of importance for regenerative medicine strategies.

Quantitative live imaging of floral organ initiation and floral meristem termination in Aquilegia.

In-depth investigation of any developmental process in plants requires knowledge of both the underpinning molecular networks and how they directly determine patterns of cell division and expansion over time. Floral meristems (FMs) produce floral organs, after which they undergo floral meristem termination (FMT); precise control of organ initiation and FMT is crucial to the reproductive success of any flowering plant. Using live confocal imaging, we characterized developmental dynamics during floral organ primordia initiation and FMT in Aquilegia coerulea (Ranunculaceae). Our results uncover distinct patterns of primordium initiation between stamens and staminodes compared with carpels, and provide insight into the process of FMT, which is discernable based on cell division dynamics that precede carpel initiation. To our knowledge, this is the first quantitative live imaging of meristem development in a system with numerous whorls of floral organs, as well as an apocarpous gynoecium. This study provides crucial information for our understanding of how the spatial-temporal regulation of floral meristem behavior is achieved in both evolutionary and developmental contexts. This article has an associated 'The people behind the papers' interview.

How does early-life adversity shape telomere dynamics during adulthood? Problems and paradigms.

Although early-life adversity has been associated with negative consequences during adulthood, growing evidence shows that such adversity can also lead to subsequent stress resilience and positive fitness outcomes. Telomere dynamics are relevant in this context because of the link with developmental conditions and longevity. However, few studies have assessed whether the effects of early-life adversity on developmental telomere dynamics may relate to adult telomere dynamics. We propose that the potential links between early-life adversity and adult telomere dynamics could be driven by developmental constraints (the Constraint hypothesis), by the nature/severity of developmental adversity (the Resilience hypothesis), or by developmental-mediated changes in individual life-history strategies (the Pace of Life hypothesis). We discuss these non-mutually exclusive hypotheses, explore future research directions, and propose specific studies to test these hypotheses. Our article aims to expand our understanding of the evolutionary role of developmental conditions on adult telomere dynamics, stress resilience and ageing.

Adult pancreatic islet endocrine cells emerge as fetal hormone-expressing cells.

SummaryThe precise developmental dynamics of the pancreatic islet endocrine cell types, and their interrelation, are unknown. Some authors claim the persistence of islet cell differentiation from precursor cells after birth (“neogenesis”). Here, using four conditional cell lineage tracing (“pulse-and-chase”) murine models, we describe the natural history of pancreatic islet cells, once they express a hormone gene, until late in life. Concerning the contribution of early-appearing embryonic hormone-expressing cells to the formation of islets, we report that adult islet cells emerge from embryonic hormone-expressing cells arising at different time points during development, without any evidence of postnatal neogenesis. We observe specific patterns of hormone gene activation and switching during islet morphogenesis, revealing that, within each cell type, cells have heterogeneous developmental trajectories. This likely applies to most maturating cells in the body, and explains the observed phenotypic variability within differentiated cell types. Such knowledge should help devising novel regenerative therapies.