Developmental Mechanisms of Neurogenesis

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Most of what we know about the embryonic development of nervous systems comes from studies of flies or mice. As those studies revealed similar signaling systems and molecular pathways, it was proposed that nervous systems arose once, early in the history of multicellular animals. Subsequent studies in several types of invertebrates support this idea, but the striking diversity in how nervous systems develop makes it difficult to rationalize a single origin. A more refined explanation is that there has been independent evolution of the cellular organization in many groups and neurogenesis has drawn upon conserved signaling systems and molecular pathways in various ways as animals diversified. We lack the models necessary to test this hypothesis, as the molecular and cellular mechanisms underlying neurogenesis need to be carefully analyzed to make useful comparisons in groups of related animals. Deuterostomes are a large grouping of animals including vertebrates and several invertebrates groups that are closely related by measurements of molecular kinship, yet have very diverse body forms. The organization of nervous systems within the deuterostomes ranges from simple to very complex. To better understand the origin and diversification of multicellular animals I have developed a research program with the long-term objective of determining the cellular and molecular mechanisms of neurogenesis in sea urchin embryos. These studies will establish a novel neurogenesis model and provide new insights into metazoan evolution. Sea urchins are echinoderms, one of the basal groups of deuterostomes, so mechanisms they employ in neurogenesis reveal fundamental features shared by all deuterostomes, and those that have arisen in more complex deuterostomes. Sea urchins have been used for 150 years to study many aspects of early development. Excellent genomic resources, simple systems for controlling gene expression, and clear embryos, conducive to imaging, make sea urchins excellent models. The proposed studies will examine dedicated neural progenitors, or neural stem cells. It will determine how Notch signaling and fibroblast growth factor (FGF) signaling function in neurogenesis. As well, it will determine if the central nervous system is patterned, or expresses certain transcription factors and has dedicated neural progenitors in specific anatomical locations. The research will use novel methods and will generate unique reagents to further use of this model. The proposed studies are excellent projects for students, and the training gives highly desired skills that ensure their further success. This research will have broad impact across disciplines, because understanding the cellular and molecular mechanisms by which embryonic cells are transformed into a complex nervous system is relevant to developmental biology, neurobiology, evolutionary biology, cell, and molecular biology.