Patricia A. Estes

Research Assistant Professor of Genetics

PhD, University of Pennsylvania
Postdoctoral, Princeton University, Duke University,
University of North Carolina at Chapel Hill
 

The Development of the Central Nervous System (CNS)

My research focuses on fundamental questions of developmental neurobiology, and particularly on how specific genes are regulated during the development of the nervous system. The system used for these studies is the early development of the Drosophila CNS midline cells. The axon scaffold of the Drosophila CNS is made up of repeating segmental units, consisting of both an anterior and posterior commissure, which connect the two bilaterally symmetric longitudinal axon tracts. Amidst the commissures and longitudinals, lie the CNS midline cells, which provide many signals to guide the paths of axons during growth. The midline cells differentiate into a diverse set of neurons and glia and all of their development is dependent upon the expression of the single-minded (sim) gene. Sim acts as a switch to direct neuroectodermal cells to a midline fate by both activating midline gene transcription and repressing lateral CNS gene transcription. Sim is a bHLH-PAS transcription factor and functions by forming a heterodimer with the Tango protein and binding to CNS midline elements (CMEs, ACGTG) within downstream target genes. At present, 52 genes are known to be expressed in midline cells, and many more must exist that have yet to be identified.

An early Drosophila embryo with the midline cells labeled in green and the cells of the lateral CNS labeled in red. The area of overlap is yellow. Soon after this point in development, the sim gene represses lateral CNS gene expression in the midline cells.

The approach is to identify the genes expressed in midline cells using microarray technology, and then to dissect their function during embryogenesis. Three novel midline genes have recently been identified with this approach and their functions in the embryo are being tested. Of particular interest are the key morphological movements that transplant the midline cells from the surface of the embryo to their location within the ventral nerve cord and the morphological events that transform the midline cells into neurons and glia. In addition, we have identified the presence of factors that repress lateral CNS genes in midline cells, and our goal is to identify these repressors with the microarrays. These studies indicate how differential gene expression leads to the development of the CNS midline cells.

The midline cells (green) in close association with the CNS axons (red) of a Drosophila embryo during mid embryogenesis.

Selected Publications:

Estes, P., Fulkerson, E., and Zhang, Y. 2008. Identification of motifs that are conserved in twelve Drosophila species and regulate midline glia versus neuron expression. Genetics (in press).

Kearney, J.B., Wheeler, S.R., Estes, P., Parente, B., Crews, S.T. 2004. Gene expression profiling of the developing Drosophila CNS midline cells. Dev Biol. 275: 473-492.

Sugimura, K., Satoh, D., Estes, P., Crews, S., and Uemura, T. 2004. Development of morphological diversity of dendrites in Drosophila by the BTB-zinc finger protein abrupt. Neuron 43: 809-822.

Estes, P.A., Mosher, J. and Crews, S.T. 2001. Drosophila single-minded represses gene transcription by activating expression of repressive factors. Dev. Biol. 232: 157-175. [Abstract]

Yang, D., Lu, H., Hong, Y., Jinks, T.M., Estes, P.A. and Erickson, J.W. 2001. Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for the basic helix-loop-helix proteins SISB and daughterless. Mol Cell Biol. 21:1581-1592. [Abstract]

Emmons, R.B., Duncan, D., Estes, P.A., Kiefel, P., Mosher, J.T., Sonnenfeld, M., Ward, M.P., Duncan, I. and Crews, S.T. 1999. The spineless-aristapedia and tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila. Development 126:3937-3945. [Abstract]

Estes, P.A., Keyes, L.N. and Schedl, P. 1995. Multiple response elements within the Sex-lethal early promoter ensure its female-specific expression pattern. Mol. Cell. Biol. 15: 904-917. [Abstract]

For more information contact:

Dr. Pat A. Estes
Department of Genetics
N.C. State University
Raleigh, NC 27695-7614
Tel: (919) 513-2718
pat_estes@ncsu.edu

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