In one of the most common patterning scenarios in animal development, signaling pathways establish domains of gene expression in two-dimensional epithelial sheets. Mutations that are associated with the abnormal development and pathologies of tissues can occur in the source of the signal (trans changes) and/or in the target genes (cis changes). These changes are often deleterious and happen over a relatively short period of time. The same changes are required during speciation. These changes occur over an evolutionary time scale. The Drosophila eggshell is an established model system to study the impact of changes in cell signaling on tissue patterning and morphogenesis. The natural diversity of eggshells among Drosophila species is an emerging area of research. The Yakoby Lab established a new model system, the dorsal ridge, a lumen-like structure on several Drosophila species eggshells. The dorsal ridge was used to study how changes in the spatiotemporal distributions of the TGF-? like ligand Gurken (GRK) change the activation pattern of the epidermal growth factor receptor (EGFR). These changes in trans control the evolution of morphological novelty, which is in contrast to most publications that focus on changes in cis regulation as the driving force behind the evolution of patterning and morphogenesis. This grant aims to study the evolution of several GRK proteins to elucidate the mechanisms of ligand distribution that ultimately control the final shape and size of the dorsal ridge (Aim 1). In addition, it is proposed to study the changes in cis regulation of Broad (BR), a master regulator of respiratory dorsal appendages, on Drosophila eggshells (Aim 2). The pattern of BR is established by an intricate network of transcription factors that are regulated by the EGFR and bone morphogenetic protein (BMP) signaling. Based on the preliminary results, it is proposed that the spatiotemporal difference in the expression patterns of the enhancer controlling the late phase of BR expression is underlying the evolution of the number of dorsal appendages on Drosophila eggshells. Thus, the combination of trans and cis changes underlie the evolution of morphogenesis. The availability of genetic and genome engineering tools together with the sequenced genomes of multiple species, make Drosophila a successful model system to study how changes in signaling and their target genes' network evolved. The Yakoby Lab pioneered the molecular study of dorsal ridge formation as a new model system. Together with their extensive experience in genetic and molecular manipulations of D. melanogaster and other Drosophila species, the Yakoby Lab is in an excellent position to study cis and trans changes that shape the evolution of eggshell morphologies.

Public Health Relevance

The evolution of morphologies has been mostly associated with change in the regulation of gene expression. We use the spatiotemporal changes of EGFR activation among Drosophila species to study the evolution eggshells? morphologies. We focus on cis and trans changes in signaling pathways and their targets to study the evolution of morphologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
2R15GM101597-02
Application #
9442378
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Hoodbhoy, Tanya
Project Start
2013-08-01
Project End
2020-08-31
Budget Start
2017-09-15
Budget End
2020-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Rutgers University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
625216556
City
Camden
State
NJ
Country
United States
Zip Code
08102
Marmion, Robert A; Yakoby, Nir (2018) In locus analysis of patterning evolution of the BMP type II receptor Wishful thinking. Development 145:
Revaitis, Nicole T; Marmion, Robert A; Farhat, Maira et al. (2017) Simple Expression Domains Are Regulated by Discrete CRMs During Drosophila Oogenesis. G3 (Bethesda) 7:2705-2718
Pyrowolakis, George; Veikkolainen, Ville; Yakoby, Nir et al. (2017) Gene regulation during Drosophila eggshell patterning. Proc Natl Acad Sci U S A 114:5808-5813
Rossi, Francesco; Duteil, Nastassia Pouradier; Yakoby, Nir et al. (2016) Control of reaction-diffusion equations on time-evolving manifolds. Proc IEEE Conf Decis Control 2016:1614-1619
Niepielko, Matthew G; Yakoby, Nir (2014) Evolutionary changes in TGF? distribution underlie morphological diversity in eggshells from Drosophila species. Development 141:4710-5
Niepielko, Matthew G; Marmion, Robert A; Kim, Kenneth et al. (2014) Chorion patterning: a window into gene regulation and Drosophila species' relatedness. Mol Biol Evol 31:154-64