# Regulation of Organ Size and Shape by Fat Signaling

> **NIH NIH R00** · UNIVERSITY OF TEXAS DALLAS · 2020 · $248,966

## Abstract

Project Summary/ Abstract
Coordination of growth and morphogenesis during development is critical for formation of organs of proper
shape and size and improperly sized and shaped organs often lead to organ malfunction and congenital
anomalies. The protocadherins, Dachsous (Ds) and Fat constitute a highly conserved signaling pathway that
regulates growth through its influence on Hippo signaling and morphogenesis by regulating planar cell polarity
and oriented cell divisions. Consistently, mutations affecting this pathway result in a number of diseases
affecting organ shape or size. Studies in Drosophila have provided important insights into the molecular
mechanisms that regulate organ size and shape by Fat signaling. Recently I have identified a new gene
Vamana, which is a critical downstream component of the Fat signaling pathway. Additionally, my recent work
has identified several novel regulators of this pathway and has led to intriguing findings that suggest that
vesicular trafficking plays a crucial role in regulating Fat signaling, an aspect that is very little explored. In Aim
1, I propose to investigate the vesicular trafficking mechanisms that organize this signaling pathway.
Specifically, I will study the interplay of ubiquitination and palmitoylation in trafficking of the components of this
pathway. From a pilot genetic screen, I have recently isolated a novel mutation, Big round wings (Brw), which
displays phenotypes characteristic of mutations in Fat-signaling pathway. In Aim 2, I will characterize how Brw,
regulates this pathway. Finally, based on the success of the pilot screen, I propose to identify additional
regulators of Fat signaling by an innovative forward gain of function screen. While my recent work has enabled
me to generate these intriguing findings and the research plan, my immediate goals are to obtain additional
training in live imaging, vesicular trafficking, ubiquitination and palmitoylation that are necessary to further
develop these projects. I have arranged a group of distinguished mentors, who will provide me with this
additional training. During the mentored phase of this award, I will train with Dr. Barth Grant to learn how to
approach and solve problems in vesicular trafficking. My mentor, Dr. Kenneth Irvine will provide training in live
imaging, and Dr. Marc Gartenberg will provide mentorship on development of the yeast based assay to identify
substrates of palmitoyl transferases. The proposed training combined with my previous research experience
will enable me to undertake a multipronged comprehensive approach to unravel novel molecular mechanisms
regulating Fat signaling. This research plan will also provide insight into pathogenesis of congenital
developmental defects arising from disruptions in Fat signaling. The pathway to independence award will
enable me to acquire the training and resources I need to achieve my immediate research goals. Further, the
proposed training and the innovative research progr...

## Key facts

- **NIH application ID:** 9995545
- **Project number:** 5R00HD092553-04
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Jyoti R. Misra
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,966
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995545

## Citation

> US National Institutes of Health, RePORTER application 9995545, Regulation of Organ Size and Shape by Fat Signaling (5R00HD092553-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9995545. Licensed CC0.

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