# Retinal Patterning During Eye Development

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $436,725

## Abstract

The function of the visual system is to form images in the brain. Correct photoreceptor neuron specification,
patterning and morphogenesis within the retina are prerequisites for correct retinotopic axonal projections and
thus image formation. The Drosophila eye serves as an excellent paradigm for many aspects of eye
development, retinal biology, and disease. It is composed of a stereo-typed array of 700-800 ommatidia, or unit
eyes/facets, each containing a precise arrangement of 8 photoreceptor neurons, R-cells. Establishment of their
fates and their ordered arrangement requires an interplay of several signaling pathways, which are conserved
with similar functions during mammalian eye development. Precise retinal arrangement and morphogenesis
requires a distinction of two subtypes of photoreceptors, R3 and R4, via an exquisite regulation and interplay of
canonical Wnt-signaling, the Wnt/Frizzled(Fz)/planar cell polarity (PCP) pathway, and Notch (N)-signaling.
Wnt/β-catenin signaling sets up the D/V-axis, needed by Wnt/Fz-PCP signaling to correctly induce R3/R4
neurons. Wnt-PCP signaling in turn has to both activate N-signaling in neighboring cells to induce R4, and
simultaneously inhibit N-activity in R3. Thus a highly regulated Wnt/Fz and N-pathway cross-regulation
determines photoreceptor patterning and morphogenesis of the retina. Our prelim. data identified a novel
cross-talk between Wnt and N-signaling at the level of Dsh/Dvl and the N-dependent transcription factor Su(H),
CSL in mammals. We have also uncovered a novel function for non-canonical N-signaling in cell adhesion and
morphogenesis, mediated by Abl kinase. The scope of this application addresses interactions among the Wnt
and N pathways and functional dissection of the non-canonical N activity in the retina. The Specific Aims are:
(1) To dissect a novel inhibitory cross-talk between the Wnt/Fz-Dsh and N-signaling and the associated effects
on R3/R4 specification; (2) To address the function of non-canonical N/Abl-signaling during retinal patterning in
R4 cell motility and ommatidial rotation; and (3) To use live imaging to extract specific roles of N/Abl signaling
in tissue morphogenesis and associated biophysical properties of cell adhesion. These Aims are well
integrated and based on exciting hypotheses and prelim. data, including analyses of several kinases and N-
signaling read-outs (Aims 1 and 2), and the role of the N/Abl activity in the regulation of junctional remodeling
and morphogenesis (Aim 3). A combination of in vivo studies, cell culture and biochemical experiments, and
genetics/genomics will be utilized together with newly developed live imaging protocols to achieve these goals.
In the human eye, Wnt-Fz and Notch signaling are associated with many diseases and, moreover, several
components are associated with congenital ciliopathies affecting retinal function. Thus the information acquired
here will advance our understanding of retinal biology and will also be of me...

## Key facts

- **NIH application ID:** 9998293
- **Project number:** 2R01EY013256-20
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Marek Mlodzik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $436,725
- **Award type:** 2
- **Project period:** 2001-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998293

## Citation

> US National Institutes of Health, RePORTER application 9998293, Retinal Patterning During Eye Development (2R01EY013256-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998293. Licensed CC0.

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