The clock and wavefront mechanisms underlying segmentation in vertebrates and the genetic hierarchy regulating segmentation in Drosophila seemingly imply independent origins of metameric development. However, comparative studies in non-drosophilid insects and other arthropods provide increasing molecular evidence for a common ancestry. In Drosophila, segments are patterned simultaneously. In most other insects including the red flour beetle Tribolium castaneum, other arthropods and vertebrates, segmentation is a longer process that occurs progressively from anterior to posterior. To understand the molecular mechanisms driving sequential metamerism and identify new genes important to this process, we are studying the genetic regulation of segmentation in Tribolium. In Tribolium, abdominal segments arise from a posterior growth zone during germband elongation, and RNAi with several early patterning genes truncates segmentation from the growth zone, suggesting this is an important regulation point. We have identified a gene circuit of primary pair-rule genes that functions to generate segments sequentially. Defects in its components disrupt the gene circuit and truncate the segmentation process. Periodic expression of two genes in this circuit initiates as twin spots in the posterior growth zone and may be regulated by early patterning genes. In addition, we have found that TcWnt8 is expressed in twin spots in the posterior growth zone, and TcWnt8 RNAi embryos are truncated in the thorax. We hypothesize that segmentation and elongation may be regulated by posterior signals that control components of the pair-rule gene circuit and/or proliferation. We will combine genetic and molecular approaches to analyze the relationship of cell proliferation, convergent extension and posterior signaling to segmentation, all of which are fundamental to embryonic elongation in vertebrates and arthropods. The genetic and genomic tools we have developed, combined with the Tribolium genome sequence, provide a unique opportunity to identify, regulatory genes and molecular processes which may represent presently unrecognized, developmentally significant mammalian counterparts important to segmentation. Our studies have the potential to provide new insight into human birth defects in spinal development and cancers related to misregulation of signaling mechanisms.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Coulombe, James N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Kansas State University
Schools of Arts and Sciences
United States
Zip Code
Choe, Chong Pyo; Stellabotte, Frank; Brown, Susan J (2017) Regulation and function of odd-paired in Tribolium segmentation. Dev Genes Evol 227:309-317
El-Sherif, Ezzat; Zhu, Xin; Fu, Jinping et al. (2014) Caudal regulates the spatiotemporal dynamics of pair-rule waves in Tribolium. PLoS Genet 10:e1004677
Fu, Jinping; Posnien, Nico; Bolognesi, Renata et al. (2012) Asymmetrically expressed axin required for anterior development in Tribolium. Proc Natl Acad Sci U S A 109:7782-6
Bao, Riyue; Fischer, Tami; Bolognesi, Renata et al. (2012) Parallel duplication and partial subfunctionalization of ýý-catenin/armadillo during insect evolution. Mol Biol Evol 29:647-62
El-Sherif, Ezzat; Lynch, Jeremy A; Brown, Susan J (2012) Comparisons of the embryonic development of Drosophila, Nasonia, and Tribolium. Wiley Interdiscip Rev Dev Biol 1:16-39
Miller, Sherry C; Miyata, Keita; Brown, Susan J et al. (2012) Dissecting systemic RNA interference in the red flour beetle Tribolium castaneum: parameters affecting the efficiency of RNAi. PLoS One 7:e47431
El-Sherif, Ezzat; Averof, Michalis; Brown, Susan J (2012) A segmentation clock operating in blastoderm and germband stages of Tribolium development. Development 139:4341-6
Robinson, Gene E; Hackett, Kevin J; Purcell-Miramontes, Mary et al. (2011) Creating a buzz about insect genomes. Science 331:1386
Brown, Sue (2010) The Nasonia genome sequence: finding gems in the jewel (wasp) box. Insect Mol Biol 19 Suppl 1:v-vii
Janssen, Ralf; Le Gouar, Martine; Pechmann, Matthias et al. (2010) Conservation, loss, and redeployment of Wnt ligands in protostomes: implications for understanding the evolution of segment formation. BMC Evol Biol 10:374

Showing the most recent 10 out of 49 publications