The Evolution of Posterior Fate

The evolution of body shape and body axes relies on changes to regulatory networks that control tissues' development across organisms. The grant will examine how changes in the regulatory network of genes in one species can be changed and lead to the formation of morphological novelties in other species. Uncovering the natural changes underlying morphological diversity among species will shed light on organ formation strategies. The preliminary results demonstrate the successful use of a genome engineering technique in non-traditional species, which will allow the principal investigator to establish them as new model systems to study how changes in gene regulation control the evolution of new morphologies. The studied signaling pathways and transcription factors are conserved in other animals, hence the Drosophila community and other developmental communities will gain knowledge on these pathways and benefit from the generated genetic tools. A Postdoctoral trainee, a Ph.D. student, and 9 undergraduate students will be trained in fly genetics, molecular biology, bioinformatics and genome engineering, with an emphasis on trainees from underrepresented minorities in the STEM fields. The data generated will be incorporated into the Genetics class curricula at the level of graduate and undergraduate studies, which serves about 60 students annually. The principal investigator will reach out to prospective biology students and their families from the Camden, NJ area during the biology visiting days.

Axis formation is a fundamental requirement during animal development. This intricate process is regulated by a small number of highly-conserved cell signaling pathways across animals. The principal investigator (PI) will study the evolution of gene regulatory networks, comprised of the epidermal growth factor receptor (EGFR), the Janus Kinase (JAK/STAT), bone morphogenetic protein (BMP), and transcriptional regulators that control the anterior posterior axis in Drosophila melanogaster. The PI suggests that components of the network evolved from controlling axis formation during fly oogenesis to also regulating the formation of a morphological novelty, the dorsal ridge, on the D. nebulosa eggshells. The PI's laboratory pioneered the molecular analysis of dorsal ridge formation by discovering the dramatic changes in EGFR activation patterns among species. The PI hypothesizes that changes in cis regulation of genes controlling the posterior fate in one species evolved to guide the generation of a new morphology in other species. The preliminary results demonstrate that the ETS-transcription factor Pointed (PNT) controls the expression of the posterior determinant Midline (Mid). Research goals are to, a) determine the network controlling patterning of the posterior end, b) study the cis regulatory modules controlling mid expression and 3), study whether changes in MID patterning control the evolution of the dorsal ridge. Using a combination of immunostaining, genetic perturbations, including CRISPR/Cas9, and reciprocal swapping of orthologous CRMs, the function, requirement, and redundancy of these CRMs will be tested for patterning and morphogenesis in both D. melanogaster and D. nebulosa.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.