Structure-function analysis of Defective proventriculus (Dve) in Drosophila melanogaster eye development

Organ development is a highly regulated process to transform a monolayer organ primordium into a fully developed organ. Formation of morphogen gradient acts as critical cue to determine cell fate in developing tissues. In Drosophila melanogaster (Fruit fly), wingless (wg) morphogen acts as a negative regulator of eye development and wg gradient determines the eye vs. head fate. Previously, we have identified defective proventriculus (dve, an ortholog of SATB1) as a novel dorsal patterning gene that regulates transcription of wg morphogen. Axial patterning is required to establish Antero-posterior (AP), Dorso-Ventral (DV), and Proximo-Distal (PD) axes. Of the three axes, DV axis is the first lineage restriction event during eye development and any deviation results in developmental birth defects. In the dorsal gene hierarchy, dve acts downstream of GATA-1 transcription factor pannier (pnr) and upstream of wg. Loss-of-function of dve results in dorsal eye enlargement and increase in wg while gain-of-function results in eye suppression and reduced wg. In humans, SATB1 functions as a transcriptional regulator and chromatin organizer and requires tetramerization by the ULD domain. Furthermore, SATB1, the human ortholog of dve is highly upregulated in cancers. Here we have used the Drosophila eye model to understand the role of different Dve protein domains. We performed structure-function analysis of Dve protein to elucidate the role of various domains in regulating wg and eye development. We have developed several transgenic lines, which will allow us to induce expression of the specific domains of Dve protein and assay their effect in the eye. Dve has a ULD domain for tetramerization, HOX domains for DNA binding and PPP4R2 domain for H2AFX dephosphorylation. Here we present our results on ectopic induction of these domains and their effect on eye phenotype and wg expression in the developing eye.https://ecommons.udayton.edu/stander_posters/3425/thumbnail.jp