The evolutionary origins of the vertebrate nervous system have been a long-standing puzzle in biology. A better understanding requires a comparative examination of neural development in strategically-chosen, closely-related animal groups. This project will investigate the structure and function of the nervous system of Hemichordates, marine worms closely related to vertebrates but with a nervous system that is completely different in its organizational principles. Making special use of the gross anatomical differences in neural organization between vertebrates and hemichordates, the investigators will test whether (in spite of these differences) there are close similarities in at least some of the molecular signals that specify how particular neural cell groups are organized and connected. These studies are expected to provide new insights into the organization and evolutionary trajectory of the vertebrate nervous system. The experiments will also lead to a clearer understanding of which elements of the vertebrate neural system have deep evolutionary precursors in other animal lineages, and which ones have come into being later on, as vertebrate brain organization became more complex. Finally, this work is expected to shed new light on the detailed function of the molecular mechanisms that pattern both vertebrate and invertebrate nervous systems.
The broad aim of this proposal is to carry out a comprehensive molecular characterization of the nervous system of the enteropneust hemichordate Saccoglossus kowalevskii, in order to identify basic organizational principles. The molecular genetic programs of early ectoderm differentiation in the directly-developing S. kowalevskii have been previously described in detail; these consist of exquisitely-conserved relative domains along the A/P axis similar to those of vertebrates. This finding leads to a puzzle; how can the ectodermal A/P program be so well conserved between enteropneusts and vertebrates when the organization of the nervous system is so different? The key to addressing this issue is to better understand the molecular genetic correlates of nervous system patterning in hemichordates. This project investigates the expression of a conserved suite of core genes already identified in bilaterians that defines important neuronal sub-populations. Transgenic approaches will also be used to investigate the morphology and projections of GABAergic and dopaminergic neurons, and to begin to identify potential sites of neural integration. Finally, local ectodermal signaling centers homologous to vertebrate brain organizers will be functionally manipulated to investigate which neuronal groups they are regulating.
