Developmental psychology | EPFL Graph Search

Developmental psychology is the scientific study of how and why humans grow, change, and adapt across the course of their lives. Originally concerned with infants and children, the field has expanded to include adolescence, adult development, aging, and the entire lifespan. Developmental psychologists aim to explain how thinking, feeling, and behaviors change throughout life. This field examines change across three major dimensions, which are physical development, cognitive development, and social emotional development. Within these three dimensions are a broad range of topics including motor skills, executive functions, moral understanding, language acquisition, social change, personality, emotional development, self-concept, and identity formation. Developmental psychology examines the influences of nature and nurture on the process of human development, as well as processes of change in context across time. Many researchers are interested in the interactions among personal charac

Molecular heterogeneity of the ganglionic eminence and its relationship to the birth of neocortical interneurons

Susan Willi Monnerat

Neocortical function and malfunction depends critically on a spectrum of inhibitory interneurons. To gain novel insight in normal brain function and mechanisms leading to diseases, such as epilepsy or schizophrenia, the knowledge about the specific functions of each interneuron type appears crucial. To date, the mystery about the diversity of neocortical interneurons remains still unresolved, even though much effort was devoted to the characterization of mature interneurons in the neocortex. Ten years ago, the discovery of the ganglionic eminence (GE) as origin of neocortical interneurons allowed a novel approach to assess their various identities, and thus prompted researchers to follow the fate of cells accommodated in this region. Despite the knowledge of the source location and its subdivision into three GEs, their molecular identity remained unknown apart from few genes, and consequently unabled the specific isolation of precursor cells. To this purpose, we performed extensive microarray analysis of the three GEs at various developmental timepoints to reveal their molecular heterogeneity and identify novel precursor cell surface markers that would enable their prospective isolation by flow cytometry and subsequent fate assessment in vitro and in vivo. Surprisingly, molecular heterogeneity of the three GEs was restricted to few differentially expressed genes. However, the differences in gene expression became more apparent at late developmental stage that may reflect the increased specification during development. Among the three GEs, the LGE and CGE resembled molecularly each other most, while the MGE and CGE were most distantly related to each other. Furthermore, our genome-wide expression study suggested that the CGE, a structure of so far controversial nature, was rather a unique structure than a fusion of the MGE and LGE. Analysis across developmental timepoints revealed that the MGE underwent tremendous changes in gene expression when compared to the differential expression existing between the homochronic MGE and cerebral cortex. In our microarray screen, we could identify Boc as a novel marker of LGE/CGE-resident precursor cells. Taking advantage of Boc that encodes a cell surface molecule, we could isolate the Boc+ cells from the GE by flow cytometry, and demonstrate that in contrast to Boc– cells, they self-renewed and differentiated into oligodendrocytes, astrocytes, and neurons, and thus identify them as progenitor cells. Furthermore, immunohistochemical studies suggested that Boc+ GE cells may correspond to radial glia, the embryonic neural stem cells. The specific expression of Boc in the LGE and CGE, but not in the MGE during their entire lifetime suggested that Boc is a reliable marker for LGE/CGE-resident precursor cells. To assess the fate of Boc+ GE cells, we performed homotypic transplantations of Boc+ and Boc– cells onto organotypic slice cultures, and observed that in contrast to Boc– cells, Boc+ cells did not migrate from the GE to the neocortex suggesting that Boc+ precursor cells of the GE do not generate neocortical interneurons. In future, additional fate-mapping studies of Boc+ GE cells, such as in vivo transplantation, should shed more light on the ability of Boc+ LGE/CGE precursor cells to generate neocortical interneurons, and dependent on the outcome serve to construct a cell-lineage tree of neocortical interneurons. Thus, Boc will remain a useful tool to investigate developmental processes underlying the generation of neocortical and/or other neurons, such as striatal neurons.

EPFL2007

In vitro endoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture

Stefano Davide Vianello

In humans, mice, and other mammals key internal organs such as the gut, the lungs, the pancreas, and the liver all derive from the same embryonic tissue: the endoderm. The development of all of these structures thus depends on a same set of early cells, and on the developmental instructions provided to them by the embryo. One approach to study what these instructions might be is to study the behaviour of endoderm cells when they can not rely on embryonic instructions. That is, when they are generated and made to develop outside of the embryo. The rationale behind this approach, widely embraced by the field of synthetic embryology, is that the unguided development of specific embryonic cell types can provide a window to the observation of intrinsic characteristics of these cells and of fundamental developmental principles which might not be executed or manifested within the regulated environment of the embryo. Accordingly, in the work here described I use gastruloids, synthetic models of development made by aggregation of mouse embryonic stem cells in vitro to characterise the developmental behaviour of endoderm cells, in the absence of embryonic cues and in the absence of the extraembryonic tissues that they would usually rely on in vivo. In the first chapter of this thesis, I provide an introduction, overview, and review of our current understanding of the developmental biology of mouse endoderm as this develops in the embryo. I also introduce gastruloids as stem-cell-based experimental systems to study developmental mechanisms in vitro, decoupled from the constraints of experimental work with animals and animal embryos. Chapter 2 is dedicated to the earliest steps of endoderm development in gastruloids. I show when and where these cells appear, and how they sort as the gastruloid starts to mature. I find that endoderm cells follow similar spatial and temporal developmental patterns as those they would follow if they were in the embryo. I notably find that they always remain in an epithelial state, even as other cell types undergo mesenchymal transition. In Chapter 3 I describe surprising dynamics of endoderm cells over time, and how they self-organise into complex architectures at the core of the gastruloids. The epithelial domain that forms is dynamic and plastic, and partitions the gastruloids into interfacing compartments. Importantly, I reveal a significant endodermal component to this in vitro system, usually considered to be unstructured and neural/mesodermal in character. In Chapter 4 I show how the core endoderm compartment that I see forming in gastruloids is patterned along the longitudinal axis of the aggregate, with different cellular identities at different anterior-posterior position of the domain. By comparison with published embryonic datasets, I identify endodermal identities corresponding to the full spectrum of those that make up the gut tube in the embryo. Specifically, I describe how most endodermal cells adopt an early intestinal fate, and how many acquire anterior foregut identities. The work described in this thesis presents gastruloids as promising in vitro systems for the study of endoderm biology, morphogenesis, and mature fate specification, filling a gap within the field of synthetic embryology. It also notably opens translational possibilities to the use of gastruloids to produce endodermal cell types which may be otherwise difficult to generate using conventional directed differentiation methods.

EPFL2022

Modeling spinal locomotor circuits for movements in developing zebrafish

Yann Roussel

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion. eLife digest The spinal cord is a column of nerve tissue that connects the brain to the rest of the body in vertebrate animals. Nerve cells in the spinal cord, called neurons, help to control and coordinate the body's movements. As the spinal cord develops, new neurons are born and new connections are made between neurons and muscles, resulting in more coordinated and skillful movements as time goes on. Zebrafish, for example, display body-bending maneuvers called coils within 24 hours of the egg being fertilized. Next, bursts of swimming movements emerge, which are driven by sporadic tail beats. These tail maneuvers become more consistent as the fish develops, and eventually result in smooth movements called beat-and-glide swimming. The groups of spinal cord neurons that appear at each stage of zebrafish development have been characterized, but it remains unclear how newly formed circuits (groups of neurons recently connected to each other) work together to produce swimming maneuvers. To answer this question, Roussel et al. simulated changes in the spinal cord that help zebrafish acquire new swimming movements as they grow. The computer models encoded neural circuits based on cell populations identified in experimental studies, and replicated swimming behaviors that emerge during the first few days of zebrafish development. Simulations tested how specific neural circuits generate the characteristic swimming movements that represent key developmental milestones in zebrafish. The results showed that adding new neurons and more cell-to-cell connections led to increasingly sophisticated swimming maneuvers. As the zebrafish spinal cord matured, the fish were better able to control the pace and duration of their swimming movements. Roussel et al. also identified specific patterns of neural activity linked to particular maneuvers. For example, tail beats switch direction when neurons on one side of the spinal cord excite neurons on the opposite side. This activity, which becomes more rhythmic, also needs to be exquisitely timed to produce and coordinate the right motion. Roussel et al.'s modelling of developmental milestones in growing zebrafish provides insights into how neural networks control movement. The computer models are among the first to accurately reproduce swimming behaviors in developing zebrafish. More experimental data could be added to the models to capture the full range of early zebrafish movements, and to further investigate how maturing spinal cord circuits control swimming. Since zebrafish and mammals have many spinal neurons in common, further research may aid our understanding of movement disorders in humans.

eLIFE SCIENCES PUBL LTD2021