Associate Professor

Ph.D., Purdue University, 1996
Postdoctoral Fellow, University of Southern California, 1996-1997
Emory University School of Medicine, 1998-2002

Program Affiliation: Molecular Biology & Genetics

Research Groups Affiliation: Cell Biology | Development | Evo-Devo | Evolution | Genetics

Phone: 812/856-2621
Fax: 812/856-1566
Email Justin

Kumar Lab website

The compound eye of the fruit fly, Drosophila melanogaster, is an excellent model system for studying such diverse topics as tissue determination, compartment boundary establishment, cell fate specification, cell proliferation and apoptosis, cell and planar polarity, signal transduction and cell-cell communication. The retina is a particularly good experimental model in part because it contains a limited number cell types that follow a precise and stereotyped mode of development. Additionally, thirty years of work has produced a detailed survey of the eye's cellular, molecular and morphological development. Eye development begins during embryogenesis when two groups of cells located at the dorso-lateral regions of the head express the Pax6 gene eyeless. The roughly 20 cells that initially express eyeless (and several other eye specification genes) will proliferate and organize themselves into a monolayer epithelial sheet called the eye-antennal imaginal disc. This disc will form the template from which the adult eye is created.

The eye imaginal discs of 1st instar larvae contain cells that are, to our inspection, completely unpatterned and undifferentiated. As the larvae undergo consecutive rounds of molting and growth the eye imaginal disc undergoes dramatic increases in cell proliferation and will eventually reach a size of nearly 20,000 cells. Overt patterning of the retina begins at the posterior margin of the eye disc when a wave of differentiation initiates and sweeps across the epithelium much like a wave sweeps across the ocean. The leading edge of this mobile compartment boundary is called the morphogenetic furrow. As the furrow passes cells are organized into unit eyes or ommatidia. Within a developing ommatidium lie twenty cells of which eight are photoreceptors and twelve are non-neuronal accessory cells. The eight photoreceptors are the first to be specified. Each ommatidium undergoes a stereotyped series of cell determination events: the R8 is specified first followed by the stepwise addition of the R2/5 pair, the R3/4 pair, the R1/6 pair and finally the R7 neuron. The non-neuronal cone and pigment cells are added to each unit eye after the specification of the photoreceptors. A revealing feature of ommatidial construction is the assembly line-like development of each unit eye: all steps of the assembly process can be observed in a single eye imaginal disc.

The main focus of my laboratory is aimed at understanding how the compound eye of the fruit fly is initially specified and then patterned. Nearly a decade of experimentation has identified a group of nuclear factors that form the eye specification or retinal determination cascade. Additionally, a number of signaling cascades have been shown to transmit instructions from the cell surface to members of this network. A wealth of genetic, molecular and biochemical data suggests that these nuclear factors and signaling pathways are part of a complicated and interwoven regulatory network. Each nuclear factor and each signaling cascade has functional orthologs in all seeing animals including vertebrates and, more importantly, several human retinal disorders are attributed to mutations within the human orthologs of the fly genes. These results and observations have suggested that these genes play a crucial role in eye specification in all seeing animals.

Excitingly, loss-of-function mutant phenotypes and forced expression assays have yielded many spectacular results. For example, removal of any member of the core eye specification cascade leads to severe if not total loss of retinal tissue. On the other hand, forced expression of these factors results in the redirection of non-retinal tissues towards an eye fate. Even more exciting is the observation that expression of several mammalian orthologs can (1) rescue loss-of-function fly mutations and (2) induce the formation of ectopic eyes. These results further the argument that the members of the retinal determination network sit atop the hierarchy of genes that regulate eye development in all seeing animals. Additionally, these findings have caused a profound rethinking of the origins of the eye and it is now accepted by most that the eye has had a monophyletic origin.

Yao, J.G., Weasner, B.M., Wang, L.H., Jang, C.C., Weasner, B.P., Tang, C.Y. Salzer, C.S., Chen, C.H., Hay, B., Sun, Y.H. and Kumar, J.P. 2008. Differential Requirements for the Pax6(5a) genes eyegone and twin of eyegone during eye development in Drosophila. Developmental Biology 315:535-551.

Weasner, B.P., Salzer, C.L. and Kumar, J.P. 2007. Sine oculis, a member of the SIX family of transcription factors directs eye development. Developmental Biology 303:756-771

Anderson, J.L., Salzer, C. and Kumar, J.P. 2006. Regulation of the Eye Specification Gene dachshund in the Developing Eye and Embryonic Head. Developmental Biology 297: 536-549

Anderson, J. L., Bhandari, R. and Kumar, J. P. 2005. A genetic screen identifies putative targets and binding partners of CREB Binding Protein (CBP) in the developing Drosophila eye. Genetics 171: 1655-1672.

Roederer, K., Cozy, L., Anderson, J. and Kumar, J.P. 2005 . A novel dominant negative mutation within the Six domain of the conserved eye specification gene sine oculis inhibits eye development in Drosophila . Developmental Dynamics 232:753-766

Weanser, B., Anderson, J. and Kumar, J.P. 2004. Eye Specification in Drosophila . Proceedings of the Indian National Science Academy 70:517-530

Kumar, J.P., Jamal, T., Doetsch, A., Turner, F.R. and Duffy, J.B 2004. CREB Binding Protein (CBP) functions at successive stages of eye development in Drosophila. Genetics 168:877-893.

Kumar, J.P., Hsiung, F., Powers, M.A., Moses, K. 2003 . Nuclear translocation of activated MAP kinase is developmentally regulated in the developing Drosophila eye. Development 130:3703-3714.

Kumar, J. P., Moses, K.   2001.   EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification.   Cell 104:687-697.

Kumar, J. P.   2001.   Signaling Pathways in Drosophila and vertebrate retinal development.   Nature Reviews Genetics 2:846-857.