Cell and Developmental Biology
During development, the c= ells of a multicellular organism differentiate into thousands of distinct cell type= s. For instance, humans develop skin, heart and brain cells, among others. The= re are two essential aspects to this process that are of particular interest t= o my work: 1) Cells must be specified so that they know what tissue and organ ty= pe to become. In part, specification is controlled by “selector genes,” which encode transcription factors that regulate tissue-speci= fic gene expression. 2) Different organs must develop in a regulated manner so = that each organ’s size and position fits into the context of the entire organism. This requires that cells in different tissues and organs communic= ate with one another via signal transduction pathways, in order to integrate gr= owth and pattern.
Remarkably, both selector= genes and signaling genes are well conserved in all metazoans. For instance, a selector gene called Pax6 is of critical importance for human eye developme= nt: mutations in Pax6 cause a birth defect called aniridia, in which the iris of the eye fails to form, resulting in blindness. Homologs of the Pax6 gene are present in all metazoans, from jellyfish to insects to mammals, and seem to specify eye fate in all of them. Because of this, we can use organisms besi= des humans to study how selector genes and signaling pathways cooperate in development. My approach utilizes the powerful genetic and molecular tools available in the fruit fly Drosophi= la melanogaster.
In the Drosophila head the eye and antenna develop right next to one another. One focus in the lab is to understand how the eye and antennal selector genes are controlled. For instance, the eye selector genes must be expressed only in the eye precursors. If eye selector genes are expressed in antennal precursors they change their fate and develop into an eye instead. Likewise, the antennal selector genes must be expressed only in the antennal precursors, because they will cause eye precursors to change their fate and develop into an antenna. We know that cell communication through some kind = of signaling pathway ensures that eye and antennal selector gene expression is kept separate. We are using genetics and histological techniques to find out what these signaling genes are and how they work.
The other focus in the lab involves two genes called dan a= nd danr, which act like eye selector = genes in that they are required to make an eye and are able to convert antennal precursors to an eye fate. Surprisingly however, they are also required for antennal development, and are able to convert leg precursors to an antennal fate. Thus, these two genes appear to “select” both eye and antennal fate. We are using genetics and molecular biology to explore how t= hese genes function, and how they interact with other eye and antennal selector genes to control both eye and antennal development.
I welcome students who are interested in how an eye gets made, and how different cell types become different from one another. We will work together to design a project that utilizes both genetic and molecular techniques to address current and relev= ant questions about cell specification.
Publications that represent the work I do:
Seo, H.-C., Curtiss, J., Mlodzik, M., and Fjose, A. Six class homeobox genes in Drosophila belong to three distinct families and are involved in head development. Mech Dev, 83, 127-139, 1999.
Curtiss= , J., and Mlodzik, M. Morphogenetic furrow initiation and progression during eye = development in Drosophila: the roles of decapentaplegic, hedgehog, and eyes absent. Development, 127, 1325-1336, 2000.
Curtiss= , J., Halder, G., and Mlodzik, M. Selector and signalling molecules cooperate in organ patterning. Nat Cell Biol., 4, E48-E52, 2002.
Emerald= , B.S., Curtiss, J., Mlodzik, M. and Cohen, S.M. distal antenna and distal antenna rela= ted encode nuclear proteins containing pipsqueak motifs involved in antenna development in Drosophila. Development, 130, 1171-1180, 2003.
Kenyon, K.L., Ranade, S.S., Curtiss, J., Mlodzik, M., and Pig= noni, F. Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head= . Dev Cell, 5, 403-414, 2003.
Curtiss= , J., and Mlodzik, M. Drosophila EGF receptor signaling affects Wingless diffusion and selector gene expression during patterning of the eye-antenna imaginal disc. Manuscript submitted, Development.
Curtiss, J., Emerald, B.S., Cohen, S.M. and Mlodzik, M= . distal antenna and distal antenna-related induce ectopic eyes and are required for= eye development in Drosophila. Manu= script in preparation (to be submitted October, 2005).