Developmental Program Research Articles

A multicellular developmental program in a close animal relative.

All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes1,2. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago3,4-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types. Our findings about the autonomous and palintomic developmental program of C. perkinsii hint that such multicellular development either is much older than previously thought or evolved convergently in ichthyosporeans.

3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization.

Nuclear three dimensional (3D) folding of chromatin structure has been linked to gene expression regulation and correct developmental programs, but little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their role in sex determination. Here, we determine the sex-specific 3D organization of the model brown alga Ectocarpus chromosomes at 2 kb resolution, by mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report that Ectocarpus interphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotransposons. The Ectocarpus chromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone proteins. We show that the sex determining region (SDR)within the U and V chromosomes are insulated and span the centromeres andwe link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of the U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element, providing insights regarding the impact of a latent giant dsDNA virus on the host genome's 3D chromosomal folding.

A history-dependent integrase recorder of plant gene expression with single-cell resolution

During development, most cells experience a progressive restriction of fate that ultimately results in a fully differentiated mature state. Understanding more about the gene expression patterns that underlie developmental programs can inform engineering efforts for new or optimized forms. Here, we present a four-state integrase-based recorder of gene expression history and demonstrate its use in tracking gene expression events in Arabidopsis thaliana in two developmental contexts: lateral root initiation and stomatal differentiation. The recorder uses two serine integrases to mediate sequential DNA recombination events, resulting in step-wise, history-dependent switching between expression of fluorescent reporters. By using promoters that express at different times along each of the two differentiation pathways to drive integrase expression, we tie fluorescent status to an ordered progression of gene expression along the developmental trajectory. In one snapshot of a mature tissue, our recorder is able to reveal past gene expression with single cell resolution. In this way, we are able to capture heterogeneity in stomatal development, confirming the existence of two alternate paths of differentiation.

Foxi1 regulates multiple steps of mucociliary development and ionocyte specification through transcriptional and epigenetic mechanisms.

Foxi1 is a master regulator of ionocytes (ISCs / INCs) across species and organs. Two subtypes of ISCs exist, and both α- and β-ISCs regulate pH- and ion-homeostasis in epithelia. Gain and loss of FOXI1 function are associated with human diseases, including Pendred syndrome, male infertility, renal acidosis and cancers. Foxi1 functions were predominantly studied in the context of ISC specification, however, reports indicate additional functions in early and ectodermal development. Here, we re-investigated the functions of Foxi1 in Xenopus laevis embryonic mucociliary epidermis development and found a novel function for Foxi1 in the generation of Notch-ligand expressing mucociliary multipotent progenitors (MPPs). We demonstrate that Foxi1 has multiple concentration-dependent functions: At low levels, Foxi1 confers ectodermal competence through transcriptional and epigenetic mechanisms, while at high levels, Foxi1 induces a multi-step process of ISC specification and differentiation. We further describe how foxi1 expression is affected through auto- and Notch-regulation, how Ubp1 and Dmrt2 regulate ISC subtype differentiation, and how this developmental program affects Notch signaling as well as mucociliary patterning. Together, we reveal novel functions for Foxi1 in Xenopus mucociliary epidermis formation, relevant to our understanding of vertebrate development and human disease.

Black Caregiver Perspectives During a Developmental Diagnostic Interview.

Despite increasing autism prevalence rates across racial and ethnic groups, research has traditionally overlooked the influence of culture on developmental diagnostic conversations. Addressing this gap in research is crucial to understanding and mitigating potential disparities in diagnostic experiences, especially among Black caregivers. Black caregivers encounter frustration and discrimination during the diagnostic process, citing dismissiveness and a lack of cultural competence from healthcare providers. To address these issues, this study centers the perspectives of Black caregivers as they participate in a developmental diagnostic program for toddlers under three years of age. This retrospective qualitative study, conducted exclusively by a Black research team, involved nineteen Black caregivers of thirteen toddlers as they participated in semi-structured interviews conducted by a multidisciplinary clinical team. The research team employed a conceptual content analysis to examine caregivers' descriptions of their children's behaviors and characteristics, as well as the factors and experiences associated with their descriptions. Caregivers provided distinct descriptions of behaviors and characteristics in the categories of language and communication, learning, and temperament, associating them with situational and dispositional factors and experiences. The findings offer valuable insights for implementing culturally responsive diagnostic practices. Additionally, these results may enhance the quality of caregiver-provider interactions during developmental assessment, leading to earlier and more accurate diagnoses for Black children.

The epigenetic impact of daily diet food choices on human health and chronic diseases

Nutrition, certain lifestyle behaviors (smoking, drug, alcohol addictions, etc.) and environment all contribute to cancer and other lines development. Similarly, epigenetic pathways are known to occur at the intersection between the generally reversible effects of lifestyle or ecological factors and the irreversible alterations that explain numerous diseases. Chemoprevention is the process of intervening in the epigenome to mitigate the detrimental effects of environmental factors or certain lifestyles before they lead to significant consequences. DNA is permanently exposed to various substances modifying both its genetic and epigenetic configuration. It’s controlled by various agents (methyl donors, sophisticated enzymes, etc.). Pesticides, artificial food additives, drugs and environmental toxins penetrating the placenta, can result in developmental program alterations and epigenetic changes in a fetus. In nutrition context, the research revealed that several foods can alter epigenetic markers. Some vitamins may alter DNA methylation patterns and histone alterations, possibly influencing gene expression and disease risk. Thus, dietary treatments may provide an epigenetic regulation, emphasizing nutrition role in preserving health and preventing illness via epigenetics Keywords: human epigenetics, epigenetic regulation of diseases, daily food ration, healthy food

The Role of Long Intergenic Noncoding RNA in Fetal Development

The role of long intergenic noncoding RNAs (lincRNAs) in fetal development has emerged as a significant area of study, challenging the traditional protein-centric view of gene expression. While messenger RNAs (mRNAs) have long been recognized for their role in encoding proteins, recent advances have illuminated the critical functions of lincRNAs in various biological processes. Initially identified through high-throughput sequencing technologies, lincRNAs are transcribed from intergenic regions between protein-coding genes and exhibit unique regulatory functions. Unlike mRNAs, lincRNAs are involved in complex interactions with chromatin and chromatin-modifying complexes, influencing gene expression and chromatin structure. LincRNAs are pivotal in regulating tissue-specific development and embryogenesis. For example, they are crucial for proper cardiac, neural, and reproductive system development, with specific lincRNAs being associated with organogenesis and differentiation processes. Their roles in embryonic development include regulating transcription factors and modulating chromatin states, which are essential for maintaining developmental programs and cellular identity. Studies using RNA sequencing and genetic knockout models have highlighted the importance of lincRNAs in processes such as cell differentiation, tissue patterning, and organ development. Despite their functional significance, the comprehensive annotation and understanding of lincRNAs remain limited. Ongoing research aims to elucidate their mechanisms of action and potential applications in disease diagnostics and therapeutics. This review summarizes current knowledge on the functional roles of lincRNAs in fetal development, emphasizing their contributions to tissue-specific gene regulation and developmental processes.

A shared developmental genetic basis for sexually antagonistic male and female adaptations in the toothed water strider

Abstract Sexual conflict can drive the divergence of male and female phenotypes and cross-species comparative analyses have documented patterns of correlated evolution of sex-specific traits that promote the evolutionary interests of the sexes. However, male–female coevolution can be highly dynamic, particularly if the male and female traits share an underlying genetic program. Here, we use water striders, a well-studied model system for sexually antagonistic coevolution, and ask whether sex-specific phenotypic adaptations covary across populations and whether they share a common developmental genetic basis. Using comparative analyses both at the population and species levels, we document an association between a derived male mate-grasping trait and a putative female antigrasping counteradaptation in the toothed water strider Gerris odontogaster. Interestingly, in several populations where males have partly lost their derived grasping trait, females have also reduced their antigrasping adaptation. We used RNAi to show that these male and female traits are both linked to a common developmental genetic program involving Hox- and sex-determination genes, despite the fact that they are different structures on different abdominal segments. Our work illustrates the dynamic nature of sexually antagonistic coevolution and suggests that the pleiotropic nature of developmental genetic programs can blur the distinction between inter- and intralocus genetic conflict.

The Different Concentrations of Applied Exogenous Sugars Widely Influence the Specificity, Significance and Physiological Relevance of Study Outcomings.

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

Depot-specific mRNA expression programs in human adipocytes suggest physiological specialization via distinct developmental programs.

Adipose tissue is distributed in diverse locations throughout the human body. Not much is known about the extent to which anatomically distinct adipose depots are functionally distinct, specialized organs, nor whether depot-specific characteristics result from intrinsic developmental programs, as opposed to reversible physiological responses to differences in tissue microenvironment. We used DNA microarrays to compare mRNA expression patterns of isolated human adipocytes and cultured adipose stem cells, before and after ex vivo adipocyte differentiation, from seven anatomically diverse adipose tissue depots. Adipocytes from different depots display distinct gene expression programs, which are most closely shared with anatomically related depots. mRNAs whose expression differs between anatomically diverse groups of depots (e.g., subcutaneous vs. internal) suggest important functional specializations. These depot-specific differences in gene expression were recapitulated when adipocyte progenitor cells from each site were differentiated ex vivo, suggesting that progenitor cells from specific anatomic sites are deterministically programmed to differentiate into depot-specific adipocytes. Many developmental transcription factors show striking depot-specific patterns of expression, suggesting that adipocytes in each anatomic depot are programmed during early development in concert with anatomically related tissues and organs. Our results support the hypothesis that adipocytes from different depots are functionally distinct and that their depot-specific specialization reflects distinct developmental programs.

Cell type and regulatory analysis in amphioxus illuminates evolutionary origin of the vertebrate head

To shed light on the enigmatic origin of the vertebrate head, our study employs an integrated approach that combines single-cell transcriptomics, perturbations in signaling pathways, and cis-regulatory analysis in amphioxus. As a representative of a basal lineage within the chordate phylum, amphioxus retains many characteristics thought to have been present in the common chordate ancestor. Through cell type characterization, we identify the presence of prechordal plate-like, pre-migratory, and migratory neural crest-like cell populations in the developing amphioxus embryo. Functional analysis establishes conserved roles of the Nodal and Hedgehog signaling pathways in prechordal plate-like populations, and of the Wnt signaling pathway in neural crest-like populations’ development. Furthermore, our trans-species transgenic experiments highlight similarities in the regulatory environments that drive neural crest-like and prechordal plate-like developmental programs in both vertebrates and amphioxus. Our findings provide evidence that the key features of vertebrate head development can be traced back to the common ancestor of all chordates.

Developmental change, bricolage, and how a lot of things develop: Mechanisms and changes in attachment across the lifespan.

Under the leadership of its founding editor, Dante Cicchetti, Development and Psychopathology has been recognized for decades as the foremost journal integrating developmental theory and clinical research programs. Contributors have often highlighted the implications of attachment theory and research for understanding developmental processes and pathways, and as a testing ground for intervention strategies. In this paper we reflect on the strengths and limitations of the traditional developmental perspective. We suggest that behavioral, cognitive, and emotional development are better understood as a process of bricolage (construction within constraints). This perspective is illustrated in an analysis of change mechanisms, and behavioral and representational changes, in attachment development from pre-locomotor infancy to later adulthood. Special emphasis is placed on ordinary learning and cognitive processes, rather than those specific to attachment, and on the roles that socialization pressures and changing circumstances play in shaping the course of attachment development.

Use of telemediated caregiver coaching to increase access to naturalistic developmental behavioral interventions within a statewide early intervention system.

Many families seek access to evidence-based therapy to support their child's learning. Naturalistic developmental behavioral intervention is a set of practices that use a child's natural motivation and interest to teach skills in everyday routines. Many families find naturalistic developmental behavioral interventions appealing and they have been proven to be effective. However, families may not be able to enroll in naturalistic developmental behavioral intervention-based programs due to the limited availability of trained service providers. Telehealth is the use of technology to engage with care providers, including doctors and therapists. Telehealth is an effective tool for improving access to services, especially for people in rural and underserved communities. Telehealth offers a way for providers to connect with families but it does not address the low numbers of trained providers. In this article, we share a statewide model developed to increase access to naturalistic developmental behavioral interventions for families while increasing training opportunities for early intervention providers. Through this model, expert consultants worked with caregivers and providers via telehealth for a brief series of visits. During these visits, consultants taught caregivers and providers strategies based in naturalistic developmental behavioral interventions. Feedback from caregivers and providers, along with improvement in child skills, show that this model was effective and acceptable.

Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.

The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes. Beta-cells face various stressors and metabolic challenges throughout life, rendering them susceptible to DNA breaks. The post-mitotic, long-lived phenotype of mature beta-cells further warrants robust maintenance of genomic integrity. Failure to resolve DNA damage during beta-cell development, therefore, can result in an unhealthy reserve of beta-cells and predispose to diabetes. Yet, the molecular mechanisms safeguarding beta-cell genomic integrity remain poorly understood. Here, we focus on the significance of DNA damage in beta-cell homeostasis and postulate how cellular expansion, epigenetic programming, and metabolic shifts during development may impact beta-cell genomic integrity and health. We discuss recent findings demonstrating a physiological role for DNA breaks in modulating transcriptional control in neurons, which share many developmental programs with beta-cells. Finally, we highlight key gaps in our understanding of beta-cell genomic integrity and discuss emerging areas of interest.

Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations

Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.

Socioeconomic Drivers of Food Insecurity Among Rural Households: Evidence from Participating Farmers in the Integrated Rice-Fish System in Ebonyi State, Nigeria

Nigeria has been facing a food crisis problem, with most of the poor population having limited access to adequate quantity and quality food. Food security reflects the stability of food supply, availability of, and access to food, and affects the amount of food consumed, which has implications for the population’s health. Thus, this study examined the socio-economic drivers of food security among smallholder rice farmers in Ebonyi State, Nigeria. Primary data was collected under the Feed the Future Innovation Lab for Fish (Integrated rice-fish farming system) funded by USAID through a three-stage sampling technique. Foster–Greer–Thorbecke (FGT) and the Endogenous Switching Regression model were applied in the data analysis. The mean per capita household food expenditure is N 2,456.42, and the food security line is N 1,026.43. The food security measure shows that 46.67 percent of the households experience the incidence of food insecurity, 24.6 percent point is the food insecurity depth, and 17.2 percent point is the severity of food insecurity. The ESR model shows that the drivers of food security are access to credit, marital status, farming experience, primary occupation, education, and farm size. The study proposed implementing more developmental programmes that focus on poverty alleviation, which should be gender inclusive with an option of credit support to the rice farmers.

Developmental and housekeeping transcriptional programs display distinct modes of enhancer-enhancer cooperativity in Drosophila

Genomic enhancers are key transcriptional regulators which, upon the binding of sequence-specific transcription factors, activate their cognate target promoters. Although enhancers have been extensively studied in isolation, a substantial number of genes have more than one simultaneously active enhancer, and it remains unclear how these cooperate to regulate transcription. Using Drosophila melanogaster S2 cells as a model, we assay the activities of more than a thousand individual enhancers and about a million enhancer pairs toward housekeeping and developmental core promoters with STARR-seq. We report that housekeeping and developmental enhancers show distinct modes of enhancer-enhancer cooperativity: while housekeeping enhancers are additive such that their combined activity mirrors the sum of their individual activities, developmental enhancers are super-additive and combine multiplicatively. Super-additivity between developmental enhancers is promiscuous and neither depends on the enhancers’ endogenous genomic contexts nor on specific transcription factor motif signatures. However, it can be further boosted by Twist and Trl motifs and saturates for the highest levels of enhancer activity. These results have important implications for our understanding of gene regulation in complex multi-enhancer developmental loci and genomically clustered housekeeping genes, providing a rationale to interpret the transcriptional impact of non-coding mutations at different loci.

ALOG/LSHs, a novel class of transcription factors: Evolutionarily conserved regulators of plant growth and development.

The ALOG/LSH group of proteins is highly conserved across plant lineage, starting from moss to higher flowering plants, suggesting their crucial role in the evolution and adaptation of land plants. The role of ALOG proteins is highly conserved in various developmental responses, such as vegetative and reproductive developmental programs. Their role in meristem identity, cotyledon development, seedling photomorphogenesis and leaf and shoot development has been relatively well established. Moreover, several key pieces of evidence suggest their role in inflorescence architecture and flower development, including male and female reproductive organs and flower colouration. Recent research has started to explore their role in stress response. Functionally, ALOG proteins have been demonstrated to act as transcriptional regulators and are considered a newly emerging class of transcription factors in plants that regulate diverse developmental and physiological processes. This review aims to stimulate discussion about their role in plant development and their role as transcription factors. It also aims to further unravel the underlying molecular mechanism by which they regulate growth and development throughout the plant lineage.

Thymic Mimetic Cells: Ontogeny as Immunology.

Medullary thymic epithelial cells (mTECs) generate immunological self-tolerance by ectopically expressing peripheral-tissue antigens (PTAs) within the thymus to preview the peripheral self to maturing Tcells. Recent work, drawing inspiration from old histological observations, has shown that subtypes of mTECs, collectively termed mimetic cells, co-opt developmental programs from throughout the organism to express biologically coherent groups of PTAs. Here, we review key aspects of mimetic cells, especially as they relate to the larger contexts of molecular, cellular, developmental, and evolutionary biology. We highlight lineage-defining transcription factors as key regulators of mimetic cells and speculate as to what other factors, including Aire and the chromatin potential of mTECs, permit mimetic cell differentiation and function. Last, we consider what mimetic cells can teach us about not only the thymus but also other tissues.

Management of neonates exposed prenatally to opioids: Impact of a developmental care program implementation

BackgroundTraditional approaches to management of neonates prenatally exposed to opioids are based on the use of pharmacotherapy (PT), adjusted to evolution of infant symptoms. Newer approaches focused on non-pharmacological care (NPC) are emerging, but there is little evidence on the active policies to implement to ensure their widespread practice. The primary objective of the study was to assess whether the implementation of a developmental care program in our neonatal medicine department had an impact on the management of these infants during hospitalization, notably exposure to NPC. MethodObservational study in a tertiary perinatal center. Data collected during hospitalization for infants with in utero opioid exposure included admission in the parents-infant unit (PIU) of the maternity ward, exposure to NPC and PT, occurrence of neonatal opioid withdrawal syndrome (NOWS), length of hospital stay (LOS) and feeding type at discharge. The impact of the intervention was measured by comparing three 6-year periods, the first preceding the implementation of a formalized developmental care program (2003–2008); the second following implementation of the program (2009–2014); the third after consolidation of the program (2015–2020). Results258 infants prenatally exposed to opioid were recorded. From the first to the third period, admission rate in the PIU was comparable (68 % to 73 %, p = 0. 95). Exposure to NPC (37 % to 84 %, p < 0.001) increased, whereas exposure to PT (40 % to 15 %, p = 0.002) and LOS (13 [9–18] days to 8 [6–11] days, p = 0.003) decreased. NOWS occurred in 141 (55 %) infants (63 % to 47 %, p = 0.10). In these infants, decrease in PT was also observed (64 % to 34 %, p = 0.02). After adjustment for perinatal confounders, hospitalization in the PIU (OR 3.23 [1.36; 7.66]; p = 0.008), and the 2015–2020 period (OR 5.11 [2.06; 12.64]; p = 0.004) were associated with absence of PT. ConclusionsAn active policy, supporting the training and warranting the practice of NPC, is essential to reduce medication usage and length of hospitalization in infants exposed in utero to opioids.