Wednesday, October 1, 2025 10/1/2025

Mechanisms regulating the plasticity of postmitotic cells in mammalian retina

Award Number: R01EY032585
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

Group Awards By:

View Award Description

Mechanisms regulating the plasticity of postmitotic cells in mammalian retina - PROJECT SUMMARY/ABSTRACT One of the promising strategies to treat retinal diseases is to generate desired neuronal types, which are damaged or lost during disease, and develop cell replacement-based therapies. A comprehensive understanding of how distinct retinal types are formed during development can greatly inform these therapeutic strategies. While mitotic retinal progenitor cells (RPCs) are thought to be intrinsically different, the fates of retinal cells are not determined in RPCs. Many newly born postmitotic cells are still plastic. It is currently not clear how newly born postmitotic cells attain their final fate states. We propose to uncover the genes and pathways that regulate fate decisions in newly born postmitotic cells during development and determine whether they can also promote cell reprogramming in adult retina. We collected genes that are enriched in newly born postmitotic cells in the retina based on published single cell RNA-seq data, and developed novel methods to study their function specifically in newly born postmitotic cells in vivo by utilizing retroviral-based genetic approach and light sheet microscopy. A zinc finger transcription factor Myt1 (Myelin transcription factor 1) was found to be enriched in newly born postmitotic cells, but not RPCs, during development; it can promote neurogenesis, especially the formation of bipolar cells, while repressing glial fate in newly born postmitotic cells at neonatal stages. We hypothesize that Myt1 ensures the neuronal fates in newly born postmitotic cells and can contribute to neuronal reprogramming in mature retina. In the proposed studies, we will test this hypothesis through two aims. In Aim1, we will elucidate the function of Myt1 in fate determination, and test the hypothesis that Myt1 promotes bipolar cell fates by titrating down, but not completely shutting down Notch signaling pathway, and by actively repressing glial genes in newly born postmitotic cells. In Aim2, we will determine whether Myt1 together with Ascl1 and Brn2 can promote direct reprogramming of Müller glial cells into neurons in mature mouse retina. Taken together, this proposal aims to elucidate the plasticity of postmitotic cells in mammalian retina. We will focus on understanding how zinc finger transcription factor Myt1 promotes specific neuronal fates in newly born postmitotic cells during development and determining whether Myt1 can enhance neuronal reprogramming from glial cells in mature retina. This work will improve our understanding of basic biology and provide new candidate genes and possibilities for the regeneration of retinal neurons. Notably, mutations in human Myt1 gene are associated with Oculo-Auriculo-Vertebral Spectrum diseases, which are developmental disorders with ocular defects such as microphthalmia. Elucidating the function of Myt1 in retinal development can also shed light on the disease mechanisms.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $401,385 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	5	7/29/2025	NON-COMPETING CONTINUATION	$401,385
														Subtotal = $401,385

Issue Date FY: 2024 ( Subtotal = $401,385 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	4	5/1/2024	NON-COMPETING CONTINUATION	$401,385
														Subtotal = $401,385

Issue Date FY: 2023 ( Subtotal = $401,385 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	3	4/20/2023	NON-COMPETING CONTINUATION	$401,385
														Subtotal = $401,385

Issue Date FY: 2022 ( Subtotal = $389,340 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	2	4/18/2022	NON-COMPETING CONTINUATION	$389,340
														Subtotal = $389,340

Issue Date FY: 2021 ( Subtotal = $402,122 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Vision Research	000	1	4/9/2021	NEW	$402,122
														Subtotal = $402,122

Grand Total All Awards = $1,995,617

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms regulating the plasticity of postmitotic cells in mammalian retina

Award Number: R01EY032585

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer