Exploring the Role of miRNAs in Craniofacial Syndromes: A Genome-Wide Approach Using Drosophila Models

Exploring the Role of miRNAs in Craniofacial Syndromes: A Genome-Wide Approach Using Drosophila Models

Presenter(s)

Mani Subramanian

Comments

1:20-1:40, LTC Forum

Description

A dorsal selector gene defective proventriculus (dve), ortholog of human SATB1, is involved in a conserved mechanism of placement spacing of eyes on the heads. During organogenesis, GATA-1 transcription factor pannier (pnr) regulates dve to determine dorsal eye fate. Among various gene regulation mechanisms for dve expression, there is no information on transcriptional regulation mediated gene silencing by microRNA (miRNAs). miRNAs are the short hairpin like structure with 20-25bp which modulates the gene expressions post-transcriptionally by binding to 3’UTR of mRNAs. To discern genetic mechanism(s) regulating dve expression, we performed a forward genetic screen using a miRNA library in Drosophila eye and identified the miR-190 family as a genetic modifier. Gain-of-function (GOF) of miR-190 results in increased eye size accompanied with increased expression domain of retinal determination genes, morphogenetic furrow marker, and reduced expression of negative regulator of eye fate markers like Wg, Hth. The increased eye size in miR-190 GOF is due to increased cell proliferation with reduced cell death. Using bioinformatic analysis, we developed a miR-190-sensor which has miR-190 binding sequence from Dve 3’UTR tagged to GFP. Targeted GOF of miR-190 in domain specific manner eliminates GFP expression, which confirms dve as a target of miR-190. Regulation of dve by miR-190 is conserved as SATB1 also showed similar mode of regulation by miR-190a in humans and GOF of both dve and SATB1, rescues eye phenotypes of miR-190 in Drosophila models. We present a new mechanism of post-transcriptional regulation of dve/SATB1 expression by miR-190/miR-190a. This study demonstrates that dysregulation of the miR-190/SATB1 pathway leads to developmental defects in humans, including hypertelorism, which is characterized by an increased interocular distance and associated facial anomalies.

Publication Date

4-23-2025

Project Designation

Independent Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Exploring the Role of miRNAs in Craniofacial Syndromes: A Genome-Wide Approach Using Drosophila Models

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