Professor of Biochemistry and Biophysics
Biology – adjunct appointment
(PhD – California Institute of Technology)
The long-term goal of our lab’s research program is to comprehensively understand the molecular basis of Drosophila CNS development. Historically, this has been a broad-based systems-oriented approach. The system we employ are the cells that populate the midline of the CNS. While small in number, the midline cells consist of a diverse array of neuronal and glial cell types, and constitutes an excellent model system for studying numerous aspects of nervous system development. My laboratory has studied the Drosophila CNS midline cells for over 25 years with special attention devoted to how transcriptional regulatory proteins control midline cell development. Much of our early work studied the Drosophila single-minded bHLH-PAS transcription factor gene, the master regulator of CNS midline cell development. Our work on single-minded led us to study additional bHLH-PAS family members to uncover the biological and biochemical properties of this interesting and highly conserved group of proteins.
In recent years, we have utilized molecular, genomic, and cellular approaches, including live imaging, to pioneer understanding ofDrosophila CNS midline development in wild-type embryos. We have generated multiple databases describing midline cell gene expression, involving a large-scale in situ hybridization screen, midline cell purification/RNA-seq transcriptomic analysis, and use of Gal4 transgenic lines to identify midline enhancers (in collaboration with Janelia Farm Research Center and the labs of Chris Doe and Gerald Rubin). We have also developed computer software programs (Twine) for bioinformatic analysis of gene regulatory sequences. Our lab is now uniquely positioned to capitalize on this knowledge and employ genetic and molecular approaches to provide mechanistic insights into a variety of developmental issues. These include revealing the regulatory circuitry controlling neuronal and glial cell fate and differentiation, axon:glial interactions, neuronal and glial cell migration, and synaptic connectivity. Recent work has focused on early patterning of midline precursors, studying how combinations of transcription factors combinatorially control midline gene expression, the formation and differentiation of the H-cell midline dopaminergic neuron, the role of Notch signaling in binary midline cell fate decisions (neuron/glial and neuronal cell fate), how midline glia are partitioned into ensheathing and non-ensheathing glial subtypes, how heterophilic adhesion proteins (Wrapper and Neurexin IV) mediate axon:glial interactions, and how a family of adhesion/signaling proteins interact to control midline cell positioning within the CNS. We are also investigating how members of multi-gene families encoding membrane proteins influence larval and adult behavior and synaptic connectivity.
Genetics, Bioinformatics, Confocal microscopy, Behavioral analysis, Transgenesis, RNA-seq, ChIP
- Pearson, J.C. and Crews, S.T. (2013). Twine: display and analysis of cis-regulatory information. Bioinformatics 29, 1690-1692.
- Manning, L., Heckscher, E.S., Purice, M.D., Roberts, J., Bennett, A.L., Kroll, J.R., Pollard, J.L., Strader, M.E., Lupton, J.R., Dyukareva, A.V., Doan, P.N., Bauer, D.M., Wilbur, A.N., Tanner, S., Kelly, J.J., Lai, S-L., Tran, K.D., Kohwi, M., Laverty, T.R., Pearson, J.C., Crews, S.T., Rubin, G.M., and Doe, C.Q. A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. Cell Rep 2, 2012, 1002-1013.
- Fontana, J.R. and Crews, S.T. Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation. Dev. Biol. 2012, 372, 131-142.
- Pearson, J.C., Watson, J.D. and Crews, S.T. Drosophila melanogaster Zelda and Single-minded collaborate to regulate an evolutionarily dynamic CNS midline cell enhancer. Dev. Biol. 2012, 366, 420-432.
- Watson, J.D. and Crews, S.T. Formation and specification of a Drosophila dopaminergic precursor cell. Development 2012, 139, 3316-3325.
- Wheeler, S.R., Pearson, J.C. and Crews, S.T. Time-lapse imaging reveals stereotypical patterns of Drosophila midline glial migration. Dev. Biol. 2012, 361, 232-244.
- Jiang L, Rogers SL, Crews ST. The Drosophila Dead end Arf-like3 GTPase controls vesicle trafficking during tracheal fusion cell morphogenesis. Dev Biol. 2007 Nov 15;311(2):487-99.
- Jiang L, Crews ST. Transcriptional specificity of Drosophila dysfusion and the control of tracheal fusion cell gene expression. J Biol Chem. 2007 Sep 28;282(39):28659-68.
- Crews ST, Brenman JE. Spineless provides a little backbone for dendritic morphogenesis. Genes Dev. 2006 Oct 15;20(20):2773-8. Review.
- Jiang L, Crews ST. Dysfusion transcriptional control of Drosophila tracheal migration, adhesion, and fusion. Mol Cell Biol. 2006 Sep;26(17):6547-56.
- Wheeler SR, Kearney JB, Guardiola AR, Crews ST. Single-cell mapping of neural and glial gene expression in the developing Drosophila CNS midline cells. Dev Biol. 2006 Jun 15;294(2):509-24.