Evolutionary Developmental Biology seminars

Suhrid Ghosh will present work on how cell mechanics and cytoskeletal dynamics shape the evolution of reproductive structures in Drosophila ovaries. Cross-species morphology, ex-vivo live imaging, perturbations of cortical tension, and newly isolated terminal-filament cells reveal how somatic-cell deformability can alter ovariole architecture and reproductive fitness.

This lecture examines the development and evolution of insect learning centres. It asks how expanded neuronal populations and cell-type diversity support the behaviour of social species such as ants. Mechanisms in insect mushroom bodies are compared with changes in the mammalian cortex.

This lecture examines genetic control of tail length using variation between deer-mouse populations and targeted experiments. It considers multiple quantitative-trait loci, the possible role of Hoxd13 expression and evidence from altered Hox13 activity. Vertebral development provides a case study of how changes in gene regulation can produce evolutionary changes in body form.

This lecture compares two approaches to the evolution of mammalian tails. It critically examines the proposed role of altered Tbxt splicing in ape tail loss, including difficulties interpreting mouse experiments. It then introduces quantitative-genetic studies of deer mice in different habitats, where several loci contribute to variation in tail length.

This lecture traces research on the mouse T locus and the Tbxt gene before examining a proposed mechanism of tail loss in apes. A repeated DNA insertion may alter splicing and protein production. The discussion asks how a small genetic change could affect development and generate a large, persistent evolutionary transformation.

Tail development provides a case study for connecting genetic change to the evolution of anatomy. This lecture introduces relevant ideas from evolutionary developmental biology and RNA splicing, then considers variation in tail presence and length across mammals. It also examines what different experimental approaches can establish about DNA, form and function.

Neil Shubin connects human anatomy to the deep evolutionary history of animal bodies. Fossils, developmental mechanisms and comparisons with living species reveal inherited patterns in limbs, nerves, muscles and organ systems. The lecture also considers how research on fishes contributes to understanding human biology and disease.

Cellular crosstalk is an essential process during brain development and is influenced by numerous factors, including cell morphology, adhesion, the local extracellular matrix and secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the proper development of the human brain. Therefore, we combine 2D and 3D in vitro human models to better understand the molecular and cellular mechanisms involved in progenitor proliferation and fate, migration and maturation of excitatory and inhibitory neurons during human brain development and tackle the causes of neurodevelopmental disorders.

Brain organization and function is a complex topic. We are good at establishing correlates of perception and behavior across forebrain circuits, as well as manipulating activity in these circuits to affect behavior. However, we still lack good models for the large-scale organization and function of the forebrain. What are the contributions of the cortex, basal ganglia, and thalamus to behavior? In addressing these questions, we often ascribe function to each area as if it were an independent processing unit. However, we know from the anatomy that the cortex, basal ganglia, and thalamus, are massively interconnected in a large network. One way to generate insight into these questions is to consider the evolution and development of forebrain systems. In this talk, I will discuss the developmental and evolutionary (comparative anatomy) data on the thalamus, and how it fits within forebrain networks. I will address questions including, when did the thalamus appear in evolution, how is the thalamus organized across the vertebrate lineage, and how can the change in the organization of forebrain networks affect behavioral repertoires.

The neocortex is considered to be the seat of higher cognitive functions in humans. During its evolution, most notably in humans, the neocortex has undergone considerable expansion, which is reflected by an increase in the number of neurons. Neocortical neurons are generated during development by neural stem and progenitor cells. Epigenetic mechanisms play a pivotal role in orchestrating the behaviour of stem cells during development. We are interested in the mechanisms that regulate gene expression in neural stem cells, which have implications for our understanding of neocortex development and evolution, neural stem cell regulation and neurodevelopmental disorders.

In most animal species including humans, commissural axons connect neurons on the left and right side of the nervous system. In humans, abnormal axon midline crossing during development causes a whole range of neurological disorders ranging from congenital mirror movements, horizontal gaze palsy, scoliosis or binocular vision deficits. The mechanisms which guide axons across the CNS midline were thought to be evolutionary conserved but our recent results suggesting that they differ across vertebrates. I will discuss the evolution of visual projection laterality during vertebrate evolution. In most vertebrates, camera-style eyes contain retinal ganglion cell (RGC) neurons projecting to visual centers on both sides of the brain. However, in fish, RGCs are thought to only innervate the contralateral side. Using 3D imaging and tissue clearing we found that bilateral visual projections exist in non-teleost fishes. We also found that the developmental program specifying visual system laterality differs between fishes and mammals. We are currently using various strategies to discover genes controlling the development of visual projections. I will also present ongoing work using 3D imaging techniques to study the development of the visual system in human embryo.

Evolutionarily, the expansion of the human neocortex accounts for many of the unique cognitive abilities of humans. This expansion appears to reflect the increased proliferative potential of basal progenitors (BPs) in mammalian evolution. Further cortical progenitors generate both glutamatergic excitatory neurons (ENs) and GABAergic inhibitory interneurons (INs) in human cortex, whereas they produce exclusively ENs in rodents. The increased proliferative capacity and neuronal subtype generation of cortical progenitors in mammalian evolution may have evolved through epigenetic alterations. However, whether or how the epigenome in cortical progenitors differs between humans and other species is unknown. Here, we report that histone H3 acetylation is a key epigenetic regulation in BP profiling of sorted BPs, we show that H3K9 acetylation is low in murine BPs and high in amplification, neuronal subtype generation and cortical expansion. Through epigenetic profiling of sorted BPs, we show that H3K9 acetylation is low in murine BPs and high in human BPs. Elevated H3K9ac preferentially increases BP proliferation, increasing the size and folding of the normally smooth mouse neocortex. Furthermore, we found that the elevated H3 acetylation activates expression of IN genes in in developing mouse cortex and promote proliferation of IN progenitor-like cells in cortex of Pax6 mutant mouse models. Mechanistically, H3K9ac drives the BP amplification and proliferation of these IN progenitor-like cells by increasing expression of the evolutionarily regulated gene, TRNP1. Our findings demonstrate a previously unknown mechanism that controls neocortex expansion and generation of neuronal subtypes. Keywords: Cortical development, neurogenesis, basal progenitors, cortical size, gyrification, excitatory neuron, inhibitory interneuron, epigenetic profiling, epigenetic regulation, H3 acetylation, H3K9ac, TRNP1, PAX6

Brains do not fossilise, but as they grow and expand during fetal and infant development, they leave an imprint in the bony braincase. Such imprints of fossilised braincases provide direct evidence of brain evolution, but the underlying biological changes have remained elusive. Combining data from fossil skulls, ancient genomes, brain imaging and gene expression helps shed light on the evolutionary changes shaping the human brain. I will highlight two examples separated by more than 3 million years: the evolution of brain growth in Lucy and her kind, and differences between modern humans and Neanderthals.

The human brain sets us apart as a species, with its size being one of its most striking features. Brain size is largely determined during development as vast numbers of neurons and supportive glia are generated. In an effort to better understand the events that determine the human brain’s cellular makeup, and its size, we use a human model system in a dish, called cerebral organoids. These 3D tissues are generated from pluripotent stem cells through neural differentiation and a supportive 3D microenvironment to generate organoids with the same tissue architecture as the early human fetal brain. Such organoids are allowing us to tackle questions previously impossible with more traditional approaches. Indeed, our recent findings provide insight into regulation of brain size and neuron number across ape species, identifying key stages of early neural stem cell expansion that set up a larger starting cell number to enable the production of increased numbers of neurons. We are also investigating the role of extrinsic regulators in determining numbers and types of neurons produced in the human cerebral cortex. Overall, our findings are pointing to key, human-specific aspects of brain development and function, that have important implications for neurological disease.

Bioluminescence, which is rare on land, is extremely common in the deep sea, being found in 80% of the animals living between 200 and 1000 m. These animals rely on bioluminescence for communication, feeding, and/or defense, so the generation and detection of light is essential to their survival. Our present knowledge of this phenomenon has been limited due to the difficulty in bringing up live deep-sea animals to the surface, and the lack of proper techniques needed to study this complex system. However, new genomic techniques are now available, and a team with extensive experience in deep-sea biology, vision, and genomics has been assembled to lead this project. This project is aimed to study three questions 1) What are the evolutionary patterns of different types of bioluminescence in deep-sea shrimp? 2) How are deep-sea organisms’ eyes adapted to detect bioluminescence? 3) Can bioluminescent organs (called photophores) detect light in addition to emitting light? Findings from this study will provide valuable insight into a complex system vital to communication, defense, camouflage, and species recognition. This study will bring monumental contributions to the fields of deep sea and evolutionary biology, and immediately improve our understanding of bioluminescence and light detection in the marine environment. In addition to scientific advancement, this project will reach K-college aged students through the development and dissemination of educational tools, a series of molecular and organismal-based workshops, museum exhibits, public seminars, and biodiversity initiatives.

Leonard Maler will focus on a specialized caudal portion of the cerebellum of teleost fish whose structure and physiology has been especially well studies to the point that we now have detailed computational analyses of its function. Idoia Quintana-Urzainqui will talk about what sharks can tell us about the evolution of the telencephalon, mainly focusing on the evolutionary expansion of the pallium and how shark embryos can hold key information to interpret the origin of the developmental processes that triggered this phenomenon.