# Regulation of tissue growth and morphogenesis by Fat cadherins

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $398,750

## Abstract

Regulation of Tissue Growth and Morphogenesis by Fat Cadherins
Project Summary
Formation of optimally functioning organs of appropriate size and shape requires precise coordination of growth
and morphogenesis during development. The evolutionarily conserved cell adhesion molecules Dachsous and
Fat coordinately regulate tissue growth and patterning by influencing Hippo signaling and planar cell polarity
respectively. Mutations in these genes give rise to devastating Van Maldergem and Hennekam syndromes
characterized by congenital developmental defects of multiple organ systems. Further, mutations in these genes
are also implicated in several cancers. However, there are critical gaps in our understanding of how they regulate
growth and morphogenetic processes. We know little about how the spatial organization of the pathway is
established and maintained and how the Ds-Fat junctions get coordinately remodeled to allow morphogenesis.
Further, we lack a coherent view of how this pathway regulates Hippo signaling. Lastly, it is not clear how Fat
regulates organ shape. To address these critical gaps, we will use the fruit fly Drosophila, which provides a
robust model system to study this pathway. Our recent work has identified several novel regulators of this
pathway and uncovered some intriguing findings, which suggest that vesicular trafficking provides an important
layer of regulation in organization of the Fat signaling pathway, an aspect that has been overlooked so far. We
will investigate how an intricate interplay between the endocytic machinery and a competitive inhibitor plays a
critical role in organization of this pathway. Further, we will investigate how the Ds-Fat junctions get remodeled
by endocytosis in a mechanosensitive manner to allow morphogenesis. We have identified a key regulatory motif
in the Fat cytoplasmic domain and its interactors, which play an important role in Fat recycling to the plasma
membrane. We will characterize how this motif regulates Fat localization at the plasma membrane. Additionally,
we will investigate how Fat regulates Hippo signaling through the atypical myosin Dachs. Finally, we will examine
how Fat signaling affects the key morphogen gradients and conduct live imaging combined with quantitative
image analysis to identify the key cellular rearrangements that mediate organ shape alterations in Fat mutants.
These studies will provide novel mechanistic insight into Fat signaling pathway and address several longstanding
questions in the field and will help explain the developmental disorders resulting from dysregulation of this
pathway.

## Key facts

- **NIH application ID:** 10929403
- **Project number:** 5R35GM142831-05
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Jyoti R. Misra
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,750
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929403

## Citation

> US National Institutes of Health, RePORTER application 10929403, Regulation of tissue growth and morphogenesis by Fat cadherins (5R35GM142831-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10929403. Licensed CC0.

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