Changes In Developmental Mechanisms Research Articles

Extreme phenotypic divergence and the evolution of development.

As analyses of developmental mechanisms extend to ever more species, it becomes important to understand not just what is conserved or altered during evolution, but why. Closely related species that exhibit extreme phenotypic divergence can be uniquely informative in this regard. A case in point is the sea urchin genus Heliocidaris, which contains species that recently evolved a life history involving nonfeeding larvae following nearly half a billion years of prior evolution with feeding larvae. The resulting shift in selective regimes produced rapid and surprisingly extensive changes in developmental mechanisms that are otherwise highly conserved among echinoderm species. The magnitude and extent of these changes challenges the notion that conservation of early development in echinoderms is largely due to internal constraints that prohibit modification and instead suggests that natural selection actively maintains stability of inherently malleable trait developmental mechanisms over immense time periods. Knowing how and why natural selection changed during the evolution of nonfeeding larvae can also reveal why developmental mechanisms do and do not change in particular ways.

Developmental Changes in Mechanisms Mediating Phosphate Homeostasis

Background Phosphate (Pi) is a multivalent ion involved in a multitude of physiological processes including the formation of hydroxyapatite, the core structural component of bone. Hydroxyapatite formation occurs rapidly early in mammalian development enabling a high rate of bone formation. In the small intestine Pi absorption can occur by a transcellular or passive paracellular pathway. Of note, paracellular ion flux is governed largely by a family of proteins known as claudins, which confer permeability to epithelia. In the kidney, Pi reabsorption occurs entirely through the transcellular route. Pathological perturbations in Pi absorption and reabsorption can result in impaired bone formation and mineralization. We therefore aimed to characterize the normal developmental progression of Pi handling in the gut and kidney to determine mechanisms by which the developing mammal establishes a positive Pi balance. Methods Gene expression was determined by real-time PCR of wild-type mice aged 1, 7 days, 14 and 28 days as well as 2, 3 and 6 months of age. Of note, mice were weaned at 22 days of age. To assess developmental changes in paracellular Pi permeability, small bowel segments were isolated from mice aged 9-14 days old or 15-17 weeks of age and Chloride-Pi diffusion potentials assessed in Ussing chambers. Results The secondary sodium-Pi transporters NaPiIIb in the intestine and NaPiIIa, NaPiIIc in the kidney all showed peak expression levels early in development and proceeded to decrease in their expression levels into adulthood. However, unlike NaPiIIb which consistently displayed high expression before weaning age, NaPiIIa and NaPiIIc expression showed a lifetime low during early suckling followed by maximum lifetime expression at 2 weeks of age. There were no specific changes in claudin expression throughout development. Consistent with this, paracellular Pi permeability did not change between 9-14 days and 15-17 months of age along the intestine. Discussion Our results suggest that the mechanism responsible for establishing a positive Pi balance in young mammals is via increased transcellular absorption/reabsorption, whereas paracellular Pi flux is unlikely a significant contributor.

A novel ecological account of prefrontal cortex functional development.

In this paper, we argue that prefrontal cortex ontogenetic functional development is best understood through an ecological lens. We first begin by reviewing evidence supporting the existing consensus that PFC structural and functional development is protracted based on maturational constraints. We then examine recent findings from neuroimaging studies in infants, early life stress research, and connectomics that support the novel hypothesis that PFC functional development is driven by reciprocal processes of neural adaptation and niche construction. We discuss implications and predictions of this model for redefining the construct of executive functions and for informing typical and atypical child development. This ecological account of PFC functional development moves beyond descriptions of development that are characteristic of existing frameworks, and provides novel insights into the mechanisms of developmental change, including its catalysts and influences. (PsycINFO Database Record

The origin of novel features by changes in developmental mechanisms: ontogeny and three-dimensional microanatomy of polyodontode scales of two early osteichthyans.

Recent advances in synchrotron imaging allow us to study the three-dimensional (3D) histology of vertebrate fossils, including microfossils (e.g. teeth and scales) of early jawed vertebrates. These microfossils can often be scanned at submicron resolution (<1 µm) because of their small size. The resulting voxel (3D pixel) stacks can be processed into virtual thin sections revealing almost every internal detail of the samples, comparable to traditional thin sections. In addition, 3D models of the internal microanatomical structures, such as embedded odontodes and vasculature, can be assembled and examined in situ. Scales of two early osteichthyans, Psarolepis romeri from the Early Devonian of China and Andreolepis hedei from the Late Silurian of Sweden, were scanned using propagation phase-contrast synchrotron X-ray microtomography (PPC-SRµCT), and 3D models of internal canal systems and buried odontodes were created from the scans. Based on these new data, we review the evolutionary origin of cosmine and its associated pore-canal system, which has been long recognized as a synapomorphy of sarcopterygians. The first odontode that appeared during growth shows almost identical morphology in the two scales, but the second odontode of the Psarolepis scale shows a distinctive morphology with several pores on the surface. It is suggested that a shift from ridge-like odontode to pore-bearing odontode was the key step in the origin of cosmine, which was then elaborated further in more-derived sarcopterygians. We perform a detailed comparison between the two scales and propose a primary homology framework to generate microanatomical characters, which can be used in the phylogenetic analysis of early osteichthyans when more 3D data become available. Our results highlight the importance of 3D data for the study of histology and ontogeny of the dermal skeleton of early jawed vertebrates, especially scales of the polyodontode type. The traditional microvertebrate collection is not only useful for biostratigraphic studies, but also preserves invaluable biological information about the growth of vertebrate hard tissues. Today, we are only beginning to understand the biological meaning of the new 3D data. The increasing availability of such data will enable, and indeed require, a complete revision of traditional palaeohistological studies on early vertebrates.

Mechanism of Developmental Change in the PLAY Project Home Consultation Program: Evidence from a Randomized Control Trial.

This investigation is a secondary analysis of data from a randomized control trial of the PLAY Home Consultation Intervention Program which was conducted with 112 preschool children with Autism Spectrum Disorders and their parents (Solomon et al. in J Dev Behav Pediatr 35:475-485, 2014). Subjects were randomly assigned to either a community standard (CS) treatment group or to the PLAY Project plus CS Treatment (PLAY). PLAY subjects received monthly parent-child intervention sessions for 1year during which parents learned how to use the rationale and interactive strategies of the Developmental, Individual-differences, Relationship-based (DIR) intervention model (Greenspan and Weider in The child with special needs: encouraging intellectual and emotional growth. DeCapo Press, Cambridge, MA, 1998) to engage in more responsive, affective and less directive interactions with their children. This investigation examined whether PLAY intervention effects on parents' style of interacting with their children as well as on children's social engagement mediated the effects of PLAY on children's autism severity as measured by ADOS calibrated severity scores. Regression procedures were used to test for mediation. There were two main findings. First the effects of PLAY on children's social engagement were mediated by the increases in parental responsiveness and affect that were promoted by PLAY. Second, the effects of PLAY on the severity children's Social Affect disorders were mediated by changes in parental responsiveness and affect; however, the effects of Responsive/Affect were mediated by the impact these variables had on children's social engagement. Results are discussed in terms of contemporary models of developmental change including the developmental change model that is the foundation for DIR.

Connecting the dots from infancy to childhood: A longitudinal study connecting gaze following, language, and explicit theory of mind

This longitudinal study tested the same children at three time points: infancy (10.5months of age), toddlerhood (2.5years of age), and early childhood (4.5years of age). At 10.5months, infants were assessed experimentally with a gaze-following paradigm. At 2.5years, children’s language skills were measured using the MacArthur–Bates Communicative Development Inventories. At 4.5years, children’s explicit theory of mind was assessed with a standard test battery. Analyses revealed that infants with higher gaze-following scores at 10.5months produced significantly more mental-state words at 2.5years and that children with more mental-state words at 2.5years were more successful on the theory-of-mind battery at 4.5years. These predictive longitudinal relationships remained significant after controlling for general language, maternal education, and nonsocial attention. The results illuminate the bridging role that language plays in connecting infants’ social cognition to children’s later understanding of others’ mental states. The obtained specificity in the longitudinal relations informs theories concerning mechanisms of developmental change.

Bandwidths for the perception of head orientation decrease during childhood

Adults use the orientation of people's heads as a cue to the focus of their attention. We examined developmental changes in mechanisms underlying sensitivity to head orientation during childhood. Eight-, 10-, 12-year-olds, and adults were adapted to a frontal face view or a 20° left or right side view before judging the orientation of a face at or near frontal. After frontal adaptation, there were no age differences in judgments of head orientation. However, after adaptation to a 20° left or right side view, aftereffects were larger and sensitivity to head orientation was lower in 8- and 10-year-olds than in adults, with no difference between 12-year-olds and adults. A computational model indicates that these results can be modeled as a consequence of decreasing neural tuning bandwidths and decreasing additive internal noise during childhood, and/or as a consequence of increasing inhibition during childhood. These results provide the first evidence that neural mechanisms underlying sensitivity to head orientation undergo considerable refinement during childhood.

Mechanisms of developmental change in infant categorization

Computational models are tools for testing mechanistic theories of learning and development. Formal models allow us to instantiate theories of cognitive development in computer simulations. Model behavior can then be compared to real performance. Connectionist models, loosely based on neural information processing, have been successful in capturing a range of developmental phenomena, in particular on-line within-task category learning by young infants. Here we describe two new models. One demonstrates how age dependent changes in neural receptive field sizes can explain observed changes in on-line category learning between 3 and 10 months of age. The other aims to reconcile two conflicting views of infant categorization by focusing on the different task requirements of preferential looking and manual exploration studies. A dual-memory hypothesis posits that within-task category learning that drives looking time behaviors is based on a fast-learning memory system, whereas categorization based on background experience and assessed by paradigms requiring complex motor behavior relies on a second, slow-learning system. The models demonstrate how emphasizing the mechanistic causes of behaviors leads to discovery of deeper, more explanatory accounts of learning and development.

Did duplication of the Tfap2 family facilitate the emergence of neural crest in evolution?

During evolution, what role does gene duplication play in the emergence of new cell types? In the phylum chordata, gene duplication has occurred and may have contributed to the emergence of vertebrate specific tissues such as neural crest (NC) and placodes. The transcription factor Activator Protein 2 (Tfap2) family provides an attractive test case because there is only one Tfap2 gene in amphioxus and multiple copies in vertebrates. Moreover, a role for Tfap2 in NC and placode induction has been shown. We find that the expression pattern of duplicated Tfap2 orthologues in vertebrates “adds up” to the expression pattern of the single copy in amphioxus, supporting the duplication degeneration complementation model of gene preservation. To test whether duplicated Tfap2 family members acquired new function prior to the emergence of NC and placode, we knocked down Tfap2 family members in zebrafish, leading to loss of NC and reducing placodes, and injected mRNA encoding amphioxus Tfap2. NC and placodes were restored in such animals, suggesting duplication of Tfap2 was not a prerequisite to the emergence of NC. Alternatively, regulatory regions of the Tfap2 gene may have been altered; we are testing this hypothesis by examining conserved tfap2 regulatory regions. These studies provide insight into changes in developmental mechanisms that accompanied the emergence of vertebrate specific cell types. Grant Funding Source: NIH GM067841-01A3

Non-Cardiomyocytes Influence the Electrophysiological Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes During Differentiation

Various types of cardiomyocytes undergo changes in automaticity and electrical properties during fetal heart development. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs), like fetal cardiomyocytes, are electrophysiologically immature and exhibit automaticity. We used hESC-CMs to investigate developmental changes in mechanisms of automaticity and to determine whether electrophysiological maturation is driven by an intrinsic developmental clock and/or is regulated by interactions with non-cardiomyocytes in embryoid bodies (EBs). We isolated pure populations of hESC-CMs from EBs by lentivirus-engineered Puromycin resistance at various stages of differentiation. Using pharmacological agents, calcium (Ca(2+)) imaging, and intracellular recording techniques, we found that intracellular Ca(2+)-cycling mechanisms developed early and contributed to dominant automaticity throughout hESC-CM differentiation. Sarcolemmal ion channels evolved later upon further differentiation within EBs and played an increasing role in controlling automaticity and electrophysiological properties of hESC-CMs. In contrast to the development of intracellular Ca(2+)-handling proteins, ion channel development and electrophysiological maturation of hESC-CMs did not occur when hESC-CMs were isolated from EBs early and maintained in culture without further interaction with non-cardiomyocytes. Adding back non-cardiomyocytes to early-isolated hESC-CMs rescued the arrest of electrophysiological maturation, indicating that non-cardiomyocytes in EBs drive electrophysiological maturation of early hESC-CMs. Non-cardiomyocytes in EBs contain most cell types present in the embryonic heart that are known to influence early cardiac development. Our study is the first to demonstrate that non-cardiomyocytes influence electrophysiological maturation of early hESC-CMs in cultures. Defining the nature of these extrinsic signals will aid in the directed maturation of immature hESC-CMs to mitigate arrhythmogenic risks of cell-based therapies.

Heterochrony in limb evolution: developmental mechanisms and natural selection

The tetrapod limb provides several examples of heterochrony-changes in the timing of developmental events. These include species differences in the sequence of skeletal chondrogenesis, in gene transcription in the developing limbs, and in the relative time at which forelimb and hind limb buds develop. Here, we examine (i) phylogenetic trends in limb heterochrony; (ii) changes in developmental mechanisms that may lead to heterochrony; and (iii) the possible role that heterochrony plays in generating adaptive traits. We analyze the published literature and present preliminary data on turtle (Emys orbicularis) and bat (Rousettus amplexicaudatus) limb development. Teleosts, marsupials, and some urodeles show extreme timing differences between forelimb (or pectoral fin) and hind limb (or pelvic fin) development; this heterochrony may, in some cases, be adaptive. Published data on limb chondrogenesis reveal sequence elements that are strongly conserved (possibly owing to constraints); and others that vary between higher taxa (for unknown reasons). We find little evidence that chondrogenic sequences are modified by selection for limb functional traits. There are a few examples of developmental mechanisms that may be modified under heterochrony to produce adaptive changes in the limb (e.g. some cases of hyperphalangy or limb reduction). In conclusion, numerous examples of limb heterochrony have been recorded. However, few cases are obviously adaptive. Indeed, current data and methodologies make it difficult to identify the developmental changes, or selective pressures, that may underlie limb heterochrony. More integrative studies, including studies of heterochrony within populations, are needed to assess the role of timing shifts in limb evolution.

Computer Simulations of Developmental Change: The Contributions of Working Memory Capacity and Long‐Term Knowledge

Increasing working memory (WM) capacity is often cited as a major influence on children's development and yet WM capacity is difficult to examine independently of long-term knowledge. A computational model of children's nonword repetition (NWR) performance is presented that independently manipulates long-term knowledge and WM capacity to determine the relative contributions of each in explaining the developmental data. The simulations show that (a) both mechanisms independently cause the same overall developmental changes in NWR performance, (b) increase in long-term knowledge provides the better fit to the child data, and (c) varying both long-term knowledge and WM capacity adds no significant gains over varying long-term knowledge alone. Given that increases in long-term knowledge must occur during development, the results indicate that increases in WM capacity may not be required to explain developmental differences. An increase in WM capacity should only be cited as a mechanism of developmental change when there are clear empirical reasons for doing so.

What We Thought We Knew and How We Came to Know It: Four Decades of Cross-Cultural Research from a Piagetian Point of View

The major tenets of Piagetian theory, such as adaptation and constructionism, are compatible with a cross-cultural approach to the study of cognitive development, but there have been significant methodological and theoretical advances over the past 40 years. Piagetian theory directly influenced three phases of cross-cultural research, ranging from absolutist to relativist. As researchers incorporated the study of contexts of development, particularly cross-cultural contexts, new methods expanded the available toolbox of approaches. Recent directions in historical research, narrative and discourse research, and cognitive developmental neuroscience have helped to shed light on processes and mechanisms of developmental change and their relationship to culture.

Thinking outside the Embryo: The Superorganism as a Model for EvoDevo Studies

Traditional model systems such as fly, mouse, and chick have formed the foundation of the EvoDevo research program. These animal systems have provided a wealth of information on the patterns and mechanisms of developmental change over large phylogenetic scales. However, the almost exclusive focus on individual embryos as model organisms has also limited the field’s ability to address the central roles that natural selection and life history adaptation play in the evolution of developmental systems. Likewise, focus on this small set of “unitary” model organisms may also constrain the explanatory reach and theoretical robustness of EvoDevo if we consider that many core developmental processes like homeostatic regulation, ontogenetic differentiation, and norms of reaction are also manifest at other levels of biological organization, such as colonial organisms. The study of social insect systems can help bridge these considerable gaps in EvoDevo’s current approach. Because social insect colonies span the fine line between simple associations of “unitary” organisms and full-fledged “superorganisms,” these systems help elucidate what kinds of processes fundamentally characterize developmental systems and their evolution. What is more, the traits of social insect colonies show high degrees of population-level variability that can be linked directly to selective factors in the environment, making them ideal systems in which to more fully integrate EcoEvoDevo approaches.

Developmental mechanisms for retinal degeneration in the blind cavefish Astyanax mexicanus

The sighted surface-dwelling (surface fish, SF) and the blind cave-living (cavefish, CF) forms of Astyanax mexicanus offer a unique opportunity to study the evolutionary changes in developmental mechanisms that lead to retinal degeneration. Previous data have shown the role of increased midline Sonic Hedgehog (Shh) signalling in cavefish eye degeneration (Yamamoto et al. [2004] Nature 431:844-847). Here, we have compared the major steps of eye development in SF and CF between 14 hours and 5 days of development. We have analyzed cell proliferation through PCNA and phospho-histone H3 staining and apoptosis through TUNEL and live LysoTracker analysis. We have assessed the expression of the major eye development signalling factors Shh and Fgf8, and the eye patterning genes Pax6, Lhx2, Lhx9, and Vax1, together with the differentiation marker GAD65. We show that eye development is retarded in CF and that cell proliferation in CF retina is proportionately similar to SF during early development, yet the retina degenerates after massive apoptosis in the lens and widespread cell death throughout the neuroretina. Moreover, and surprisingly, the signalling, patterning, and differentiation processes leading to the establishment of retinal layers and cell types happen almost normally in CF, although some signs of disorganization, slight heterochronies, and a lack of expression gradients are observable. Our data demonstrate that the evolutionary process of eye degeneration in the blind CF does not occur because of patterning defects of the retina and are consistent with the proposed scenario in which the trigger for eye degeneration in CF is lens apoptosis.

Evolution of axial patterning in elongate fishes

Within the ray-finned fishes, eel-like (extremely elongate) body forms have evolved multiple times from deeper-bodied forms. Previous studies have shown that elongation of the vertebral column may be associated with an increase in the number of vertebrae, an increase in the length of the vertebral centra, or a combination of both. Because the vertebral column of fishes has at least two anatomically distinct regions (i.e. abdominal and caudal), an increase in the number and relative length of the vertebrae could be region-specific or occur globally across the length of the vertebral column. In the present study, we recorded vertebral counts and measurements of vertebral aspect ratio (vertebral length/width) from museum specimens for 54 species representing seven groups of actinopterygian fishes. We also collected, from published literature, vertebral counts for 813 species from 14 orders of actinopterygian and elasmobranch fishes. We found that the number of vertebrae can increase independently in the abdominal and caudal regions of the vertebral column, but changes in aspect ratio occur similarly in both regions. These findings suggest that abdominal vertebral number, caudal vertebral number, and vertebral aspect ratio are controlled by separate developmental modules. Based on these findings, we suggest some candidate developmental mechanisms that may contribute to vertebral column patterning in fishes. Our study is an example of how comparative anatomical studies of adults can generate testable hypotheses of evolutionary changes in developmental mechanisms. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 90 , 97‐116.

Mothers provide differential feedback to infants' prelinguistic sounds

Few studies have focused on mechanisms of developmental change during the prelinguistic period. The lack of focus on early vocal development is surprising given that maternal responsiveness to infants during the first two years has been found to influence later language development. In addition, in a variety of species, social feedback is essential for vocal development. Previous research demonstrated that maternal feedback to prelinguistic vocalizations influenced the production of more developmentally advanced vocalizations, suggesting that effects of maternal responsiveness on vocal development may start during the prelinguistic phase; however, because mothers were instructed how and when to respond to their infants' vocalizations, the timing and type of typical maternal feedback is unknown. In the present study, we analyzed unstructured play sessions for 10 mother–infant dyads to explore the relationship between prelinguistic vocal production and maternal responsiveness. Mothers responded contingently to prelinguistic vocalizations over 70% of the time. Mothers responded with more vocal responses compared to interactive responses (e.g., gazes, smiling, physical contact). Investigation of specific types of vocal responses revealed that mothers responded mainly with acknowledgments to both vowel-like sounds and consonant–vowel clusters. Mothers also showed differential responding to vocalizations that varied in quality. Mothers responded with play vocalizations to vowel-like vocalizations significantly more than to consonant–vowel clusters, whereas they responded with imitations to consonant–vowel clusters more than to vowel-like sounds. Mothers, therefore, appeared to regulate their contingent feedback relative to the speech-like quality of infants' vocalizations which may provide relevant stimulation to guide communicative development.

Continuing the discourse on the contribution of biomechanics to understanding motor development: response to the commentaries

This article continues the exploration of the usefulness of the techniques of biomechanics to understand the processes of motor development and emerging motor control. In response to commentaries on Jensen (this issue), we reiterate the importance of theory in shaping developmental hypotheses while acknowledging the divergence of opinion on the relative merits of specific biomechanical analyses. Emerging from these discussions is a consensus on the power of the techniques of biomechanics to provide more than mere description and to illuminate mechanisms of developmental change. Copyright # 2005 John Wiley & Sons, Ltd.

Evo-Devo: evolutionary developmental mechanisms.

Evolutionary developmental biology (Evo-Devo) as a discipline is concerned, among other things, with discovering and understanding the role of changes in developmental mechanisms in the evolutionary origin of aspects of the phenotype. In a very real sense, Evo-Devo opens the black box between genotype and phenotype, or more properly, phenotypes as multiple life history stages arise in many organisms from a single genotype. Changes in the timing or positioning of an aspect of development in a descendant relative to an ancestor (heterochrony and heterotopy) were two evolutionary developmental mechanisms identified by Ernst Haeckel in the 1870s. Many more have since been identified, in large part because of our enhanced understanding of development and because new mechanisms emerge as development proceeds: the transfer from maternal to zygotic genomic control; cell-to-cell interactions; cell differentiation and cell migration; embryonic inductions; functional interactions at the tissue and organ levels; growth. Within these emergent processes, gene networks and gene cascades (genetic modules) link the genotype with morphogenetic units (cellular modules, namely germ layers, embryonic fields or cellular condensations), while epigenetic processes such as embryonic inductions, tissue interactions and functional integration, link morphogenetic units to the phenotype. Evolutionary developmental mechanisms also include interactions between individuals of the same species, individuals of different species, and species and their biotic and/or abiotic environment. Such interactions link ecological communities. Importantly, there is little to distinguish the causality that underlies these interactions from that which underlies inductive interactions within embryos.

Theory of the growth and evolution of feather shape.

We present the first explicit theory of the growth of feather shape, defined as the outline of a pennaceous feather vane. Based on a reanalysis of data from the literature, we propose that the absolute growth rate of the barbs and rachis ridges, not the vertical growth rate, is uniform throughout the follicle. The growth of feathers is simulated with a mathematical model based on six growth parameters: (1) absolute barb and rachis ridge growth rate, (2) angle of helical growth of barb ridges, (3) initial barb ridge number, (4) new barb ridge addition rate, (5) barb ridge diameter, and (6) the angle of barb ramus expansion following emergence from the sheath. The model simulates growth by cell division in the follicle collar and, except for the sixth parameter, does not account for growth by differentiation in cell size and shape during later keratinization. The model can simulate a diversity of feather shapes that correspond closely in shape to real feathers, including various contour feathers, asymmetrical feathers, and even emarginate primaries. Simulations of feather growth under different parameter values demonstrate that each parameter can have substantial, independent effects on feather shape. Many parameters also have complex and redundant effects on feather shape through their influence on the diameter of the follicle, the barb ridge fusion rate, and the internodal distance. Simulated isochrones-the loci, or sets, of feather cells of the same age-have the same oblique chevron-shaped position in the mature feather as fault bars, which are isochronic defects in the barbules created by a disruptions during development. Accurate simulation of fault bar shape and position confirms the uniform absolute growth rate hypothesis and the general realism of the model. The theory defines a six-parameter feather morphospace, and provides many predictions about the developmental determination of feather shape that can be tested with detailed observations and experiments on developing feathers. This theory also provides testable predictions about the changes in developmental mechanisms required to evolve different feather shapes to accomplish various functions.