Developmental Incongruity as a Dynamical Representation of Heterochrony

Developmental Time ◽

Sequential Patterns ◽

Developmental Timing ◽

Local Computation ◽

Differential Growth ◽

Animal Development

AbstractThe theory of heterochrony provides us with a generalized quantitative perspective on the dynamics of developmental trajectories. While useful, these linear developmental trajectories merely characterize changes in the speed and extent of growth in developmental time. One open problem in the literature involves how to characterize developmental trajectories for rare and incongruous modes of development. By combining nonlinear mathematical representations of development with models of gene expression networks (GRNs), the dynamics of growth given the plasticity and complexity of developmental timing are revealed. The approach presented here characterizes heterochrony as a dynamical system, while also proposing a computational motif in GRNs called triangular state machines (TSMs). TSMs enable local computation of phenotypic enhancement by producing nonlinear and potentially unexpected outputs. With a focus on developmental timing and a focus on sequential patterns of growth, formal techniques are developed to characterize delays and bifurcations in the developmental trajectory. More generally, growth is demonstrated using two conceptual models: a Galton board representing axial symmetry and a radial tree depicting differential growth. These techniques take into consideration the existence of multiple developmental genotypes operating in parallel, which ultimately characterize the exquisite phenotypic diversity observed in animal development.

From a molar to a molecular approach to the developmental trajectory of syntax comprehension by persons with intellectual disability

10.31234/osf.io/vsu7x ◽

2020 ◽

Author(s):

Bruno Facon

Keyword(s):

Typically Developing ◽

Cognitive Level ◽

Cross Sectional ◽

Test Items ◽

Complex Sentences ◽

Regression Curves ◽

Cognitive Measure ◽

Syntactic Skills

The aim was to investigate whether a progressive dissociation between the cognitive level and syntax comprehension occurs during the development of persons with intellectual disabilities (ID). Two cross-sectional developmental trajectory analyses were successively conducted. Study 1 comprised 615 typically developing participants and 615 participants with ID. Their total scores on a syntax comprehension test were regressed on a nonverbal cognitive measure and the slopes of the two groups’ regression lines were compared. In Study 2, logistic regression curves of the two groups for each of the 92 test items were compared. Results showed only negligible between-groups differences of developmental trajectories, whatever the level of analysis. The idea of a progressive dissociation between cognitive level and receptive syntactic skills of people with ID is not confirmed. However, a syntax test evaluating more complex sentences than those used in this study might show such a dissociation.

Cognitive and School Functioning in Children and Adolescents with Chronic Pain: A Critical Review

Pain Research and Management ◽

10.1155/2010/354812 ◽

2010 ◽

Vol 15 (4) ◽

pp. 238-244 ◽

Cited By ~ 50

Author(s):

Bruce D Dick ◽

Rebecca Pillai Riddell

Keyword(s):

Chronic Pain ◽

Cognitive Function ◽

Children And Adolescents ◽

School Attendance ◽

Critical Factor ◽

Future Research ◽

Research Directions ◽

Future Research Directions

Cognitive function is a critical factor related to a child’s overall developmental trajectory. There is increasing evidence that chronic pain disrupts cognitive function in adults. Little is known about the nature or impact of cognitive disruption in children and adolescents with chronic pain. The present review examines the current literature related to cognitive function in children and adolescents with chronic pain, implications of these findings and future research directions. Nine studies on this topic were found, with a relatively recent increase in publications related to school attendance and subjective studies of school performance. The studies that were found on this topic suggested that chronic pain affects cognitive function in children but the scope of these effects on children’s function and developmental trajectories is not yet clear. While methodological issues surely make it difficult to study cognitive function in children with chronic pain, the potential gains from such research warrant a pursuit of such work. Much remains to be studied on this important topic.

Multidimensional brain-age prediction reveals altered brain developmental trajectory in psychiatric disorders

10.1101/2020.12.24.424350 ◽

2020 ◽

Author(s):

Xin Niu ◽

Alexei Taylor ◽

Russell T. Shinohara ◽

John Kounios ◽

Fengqing Zhang

Keyword(s):

Psychiatric Disorders ◽

Robust Regression ◽

Brain Structures ◽

Brain Regions ◽

Imaging Features ◽

Neuroimaging Data ◽

Brain Age ◽

Age Prediction

AbstractBrain regions change in different ways and at different rates. This staggered developmental unfolding is determined by genetics and postnatal experience and is implicated in the progression of psychiatric and neurological disorders. Neuroimaging-based brain-age prediction has emerged as an important new approach for studying brain development. However, the unidimensional brain-age estimates provided by previous methods do not capture the divergent developmental trajectories of various brain structures. Here we propose and illustrate an analytic pipeline to compute an index of multidimensional brain-age that provides regional age predictions. First, using a database of 556 subjects that includes psychiatric and neurological patients as well as healthy controls we conducted robust regression to characterize the developmental trajectory of each MRI-based brain-imaging feature. We then utilized cluster analysis to identify subgroups of imaging features with a similar developmental trajectory. For each identified cluster, we obtained a brain-age prediction by applying machine-learning models with imaging features belonging to each cluster. Brain-age predictions from multiple clusters form a multidimensional brain-age index (MBAI). The MBAI is more sensitive to alterations in brain structures and captured distinct regional change patterns. In particular, the MBAI provided a more flexible analysis of brain age across brain regions that revealed changes in specific structures in psychiatric disorders that would otherwise have been combined in a unidimensional brain age prediction. More generally, brain-age prediction using a subset of homogeneous features circumvents the curse of dimensionality in neuroimaging data.

Generation of shape complexity through tissue conflict resolution

eLife ◽

10.7554/elife.20156 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 36

Author(s):

Alexandra B Rebocho ◽

Paul Southam ◽

J Richard Kennaway ◽

J Andrew Bangham ◽

Enrico Coen

Keyword(s):

Conflict Resolution ◽

Growth Pattern ◽

Tissue Level ◽

Differential Growth ◽

Animal Development ◽

Cellular Analysis ◽

Out Of Plane ◽

Polarity Field ◽

Shape Complexity ◽

Tissue Deformations

Out-of-plane tissue deformations are key morphogenetic events during plant and animal development that generate 3D shapes, such as flowers or limbs. However, the mechanisms by which spatiotemporal patterns of gene expression modify cellular behaviours to generate such deformations remain to be established. We use the Snapdragon flower as a model system to address this problem. Combining cellular analysis with tissue-level modelling, we show that an orthogonal pattern of growth orientations plays a key role in generating out-of-plane deformations. This growth pattern is most likely oriented by a polarity field, highlighted by PIN1 protein localisation, and is modulated by dorsoventral gene activity. The orthogonal growth pattern interacts with other patterns of differential growth to create tissue conflicts that shape the flower. Similar shape changes can be generated by contraction as well as growth, suggesting tissue conflict resolution provides a flexible morphogenetic mechanism for generating shape diversity in plants and animals.

Germ-layer commitment and axis formation in sea anemone embryonic cell aggregates

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1711516115 ◽

2018 ◽

Vol 115 (8) ◽

pp. 1813-1818 ◽

Cited By ~ 10

Author(s):

Anastasia Kirillova ◽

Grigory Genikhovich ◽

Ekaterina Pukhlyakova ◽

Adrien Demilly ◽

Yulia Kraus ◽

...

Keyword(s):

Normal Development ◽

Embryonic Cell ◽

Sea Anemone ◽

Nematostella Vectensis ◽

Axis Formation ◽

Cell Aggregates ◽

Embryonic Cells ◽

Developmental Context

Robust morphogenetic events are pivotal for animal embryogenesis. However, comparison of the modes of development of different members of a phylum suggests that the spectrum of developmental trajectories accessible for a species might be far broader than can be concluded from the observation of normal development. Here, by using a combination of microsurgery and transgenic reporter gene expression, we show that, facing a new developmental context, the aggregates of dissociated embryonic cells of the sea anemone Nematostella vectensis take an alternative developmental trajectory. The self-organizing aggregates rely on Wnt signals produced by the cells of the original blastopore lip organizer to form body axes but employ morphogenetic events typical for normal development of distantly related cnidarians to re-establish the germ layers. The reaggregated cells show enormous plasticity including the capacity of the ectodermal cells to convert into endoderm. Our results suggest that new developmental trajectories may evolve relatively easily when highly plastic embryonic cells face new constraints.

Advances in Early Childhood and K-12 Education - Physical Education Initiatives for Early Childhood Learners ◽

The Cascading Effects of Gross Motor Development and the Impact of Intervention in Early Childhood

10.4018/978-1-7998-7585-7.ch001 ◽

2021 ◽

pp. 1-15

Author(s):

Ali S. Brian

Keyword(s):

Early Childhood ◽

Physical Education ◽

School Readiness ◽

Motor Development ◽

Gross Motor ◽

Cascading Effects ◽

Secular Decline ◽

Developmental Domains

Today's preschoolers are facing a secular decline with their motor development. Intervention, via physical education in preschool, can be effective to remediate gross motor delays. Teachers need ongoing support in order to intervene. If teachers intervene, children may be placed onto a positive developmental trajectory towards lifespan health. Children's gains in gross motor can transcend into other domains of development. Thus, the author urges early childhood policymakers to strongly consider hiring a licensed physical educator to implement daily physical education to preschoolers to maximize positive developmental trajectories of health. If these policy changes do not occur, children may continue on their secular decline with deleterious consequences across multiple developmental domains and school readiness.

3279 First in Man

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.107 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 45-45

Author(s):

Laura Adang ◽

Francesco Gavazzi ◽

Valentina De Giorgis ◽

Micaela De Simone ◽

Elisa Fazzi ◽

...

Keyword(s):

Skill Acquisition ◽

Classification System ◽

Spastic Paraparesis ◽

Altered Mental Status ◽

Global Developmental Delay ◽

P Value ◽

Kaplan Meier ◽

Neurologic Disability

OBJECTIVES/SPECIFIC AIMS: A mimic of congenital infections and a rare genetic cause of interferon overproduction, Aicardi Goutières Syndrome (AGS) results in significant neurologic disability. AGS is caused by pathogenic changes in the intracellular nucleic acid sensing machinery (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1). All affected individuals exhibit neurologic impairment: from mild spastic paraparesis to severe tetraparesis and global developmental delay. We hypothesize that genotype influences the heterogeneous developmental trajectory found in AGS. METHODS/STUDY POPULATION: To characterize this spectrum, age and symptoms at presentation and longitudinal developmental skill acquisition was collected from an international cohort of children (n=88) with genetically confirmed AGS. RESULTS/ANTICIPATED RESULTS: We found that individuals present at variable ages, with the largest range in SAMHD1, ADAR, and IFIH1. There are 3 clusters of symptoms at presentation: altered mental status (irritability or lethargy), systemic inflammatory symptoms, and acute neurologic symptoms, with variability across all genotypes. By creating Kaplan-Meier curves for developmental milestones, we were able to create genotype-based developmental trajectories for the children affected by the 5 most common genotypes: TREX1, IFIH1, SAMHD1, ADAR, and RNASEH2B. Individuals with AGS secondary to TREX1 were the most severely affected, significantly less likely to reach milestones compared to the other genotypes, including head control, sitting, and nonspecific mama/dada (p-value <0.005). Individuals affected by SAMHD1, IFIH1, and ADAR collectively attained the most advanced milestones, with 44% of the population achieving a minimum of a single word and 31% able to walk independently. Three retrospective scales were also applied: Gross Motor Function Classification System, Manual Ability Classification Scale, and Communication Function Classification System. Within each genotypic cohort, there was pronounced heterogeneity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results demonstrate the influence of genotype on early development, but also suggest the importance of other unidentified variables. These results underscore the need for deep phenotyping to better characterize subcohorts within the AGS population.

Developmental trajectory of prehematopoietic stem cell formation from endothelium

Blood ◽

10.1182/blood.2020004801 ◽

2020 ◽

Vol 136 (7) ◽

pp. 845-856 ◽

Cited By ~ 11

Author(s):

Qin Zhu ◽

Peng Gao ◽

Joanna Tober ◽

Laura Bennett ◽

Changya Chen ◽

...

Keyword(s):

Single Cell ◽

Fetal Liver ◽

Cell Formation ◽

Intermediate Stage ◽

Chromatin Accessibility ◽

Small Population ◽

Mammalian Embryo ◽

Hematopoietic Stem

Abstract Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.5 days post coitus (dpc) to 11.5 dpc mouse embryos by single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing. We identified a continuous developmental trajectory from E to HE to IAC cells, with identifiable intermediate stages. The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. A distal candidate Runx1 enhancer exhibits high chromatin accessibility specifically in pre-HE cells at the bottleneck, but loses accessibility thereafter. Distinct developmental trajectories within IAC cells result in 2 populations of CD45+ HSPCs; an initial wave of lymphomyeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs). This multiomics single-cell atlas significantly expands our understanding of pre-HSC ontogeny.

Functional reorganization in the developing lexicon: separable and changing influences of lexical and phonological variables on children's fast-mapping

Journal of Child Language ◽

10.1017/s0305000911000444 ◽

2012 ◽

Vol 40 (2) ◽

pp. 307-335 ◽

Cited By ~ 14

Author(s):

CRISTINA MCKEAN ◽

CAROLYN LETTS ◽

DAVID HOWARD

Keyword(s):

Word Learning ◽

Fast Mapping ◽

Lexical Knowledge ◽

Phonotactic Probability ◽

Cross Sectional ◽

Functional Reorganization ◽

Phonological Knowledge ◽

English Speaking

ABSTRACTNeighbourhood Density (ND) and Phonotactic Probability (PP) influence word learning in children. This influence appears to change over development but the separate developmental trajectories of influence of PP and ND on word learning have not previously been mapped. This study examined the cross-sectional developmental trajectories of influence of PP and ND on fast-mapping in thirty-eight English-speaking children aged 3 ; 01–5 ; 02, in a task varying PP and ND orthogonally. PP and ND exerted separable influences on fast-mapping. Overall, low ND supported better fast-mapping. The influence of PP changed across the developmental trajectory, ‘switching’ from a high to a low PP advantage. A potential explanation for this ‘switch’ is advanced, suggesting that it represents functional reorganization in the developing lexicon, which emerges from changes in the developing lexicon, as phonological knowledge is abstracted from lexical knowledge, over development.

In silico analysis identifies a putative cell-of-origin for BRAF fusion-positive cerebellar pilocytic astrocytoma

PLoS ONE ◽

10.1371/journal.pone.0242521 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242521

Author(s):

Subhi Talal Younes ◽

Betty Herrington

Keyword(s):

Gene Expression ◽

Progenitor Cells ◽

Pilocytic Astrocytoma ◽

Mapk Pathway ◽

Ventricular Zone ◽

Expression Patterns ◽

In Silico Analysis ◽

Cell Of Origin

Childhood cancers are increasingly recognized as disorders of cellular development. This study sought to identify the cellular and developmental origins of cerebellar pilocytic astrocytoma, the most common brain tumor of childhood. Using publicly available gene expression data from pilocytic astrocytoma tumors and controlling for driver mutation, a set of developmental-related genes which were overexpressed in cerebellar pilocytic astrocytoma was identified. These genes were then mapped onto several developmental atlases in order to identify normal cells with similar gene expression patterns and the developmental trajectory of those cells was interrogated. Eight known neuro-developmental genes were identified as being expressed in cerebellar pilocytic astrocytoma. Mapping those genes or their orthologs onto mouse neuro-developmental atlases identified overlap in their expression within the ventricular zone of the cerebellar anlage. Further analysis with a single cell RNA-sequencing atlas of the developing mouse cerebellum defined this overlap as occurring in ventricular zone progenitor cells at the division point between GABA-ergic neuronal and glial lineages, a developmental trajectory which closely mirrors that previously described to occur within pilocytic astrocytoma cells. Furthermore, ventricular zone progenitor cells and their progeny exhibited evidence of MAPK pathway activation, the paradigmatic oncogenic cascade known to be active in cerebellar pilocytic astrocytoma. Gene expression from developing human brain atlases recapitulated the same anatomic localizations and developmental trajectories as those found in mice. Taken together, these data suggest this population of ventricular zone progenitor cells as the cell-of-origin for BRAF fusion-positive cerebellar pilocytic astrocytoma.