Prof. Seema Agarwala
Office: PAT 406
phone: (512) 232-4797
Seema Agarwala received her Ph.D. from the State University of New York, Stony Brook in 1990. After completing her postdoctoral training at the University of Wisconsin-Madison and then at the University of Chicago, Dr. Agarwala has recently joined the faculty at the University of Texas, Austin. During her career Dr. Agarwala has received a number of awards for excellence in academics, including a prestigious award for ranking amongst the top four students in the department of Physiology at Calcutta University and a Sigma-Xi grant-in-aid of research during her graduate years. More recently, her work has twice earned her awards from the Brain Research Foundation for excellence in postdoctoral research at the University of Chicago.
Patterning of the Vertebrate Brain
During development, the vertebrate nervous system which begins as a simple sheet of undifferentiated cells, is rapidly and dramatically transformed into an immensely complex structure: the vertebrate brain. During this process, undifferentiated neuronal precursors acquire distinct cell-fates and aggregate at stereotypic positions into three-dimensional clusters called brain nuclei. These brain nuclei govern circuitry and therefore serve as a fundamental unit of brain function. The principal focus of my laboratory is to understand how this complex patterning (cell-fate specification and brain nucleogenesis) is achieved during the development of the vertebrate neural tube.
Cell fate-specification within a developing system (e.g. the nervous system) appears to depend on a mere half- dozen families of developmental control genes called signaling molecules, which are capable of turning on distinct transcriptional machinery in different groups of cells to instruct them of their cell-fates. We have found that members of each of these signaling molecules are expressed in the ventral part of the chick midbrain. Interestingly, in the chick ventral midbrain, combinations of transcription factors identify a periodic pattern of molecularly distinct stripes (midbrain arcs). This arcuate pattern is controlled in part by the signaling molecule sonic hedgehog (SHH) and precedes the formation of midbrain nuclei. Thus midbrain arcs may serve as a patterning template within which signaling molecules can act to specify cell and nuclear fates.
To explore this hypothesis, we have begun manipulation experiments with identified signaling molecules and transcription factors that could influence patterning within the ventral midbrain. These manipulations include gene misexpression by electroporation, protein misexpression using coated-beads, tissue transplantation and cell-lineage studies in vivo and in organotypic cultures. One major focus is on the morphogenetic and transcriptional control of nucleogenesis within individual arcs (e.g. motor neuron, red nucleus and dopaminergic neuron formation within the medial arc) and the role of timing in establishing cellular and nuclear fates. Manipulations in the chick are complemented with analyses of mutant mouse lines in order to identify key genes involved in the transcriptional cascades to govern nucleogenesis. A second, emerging area of interest in the laboratory is the parcellation of the dorsal midbrain into superior and inferior colliculi and to understand the molecular bases of establishing tonotopy in the inferior colliculus.