Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis

Nozomu Takata, Jason M. Miska, Marc A. Morgan, Priyam Patel, Leah K. Billingham, Neha Joshi, Matthew J. Schipma, Zachary J. Dumar, Nikita R. Joshi, Alexander V. Misharin, Ryan B. Embry, Luciano Fiore, Peng Gao, Lauren P. Diebold, Gregory S. McElroy, Ali Shilatifard, Navdeep S. Chandel and Guillermo Oliver ()
Additional contact information
Nozomu Takata: Northwestern University
Jason M. Miska: Northwestern University Feinberg School of Medicine
Marc A. Morgan: Northwestern University Feinberg School of Medicine
Priyam Patel: Northwestern University
Leah K. Billingham: Northwestern University Feinberg School of Medicine
Neha Joshi: Northwestern University
Matthew J. Schipma: Northwestern University
Zachary J. Dumar: Northwestern University Feinberg School of Medicine
Nikita R. Joshi: Northwestern University, Feinberg School of Medicine
Alexander V. Misharin: Northwestern University, Feinberg School of Medicine
Ryan B. Embry: Northwestern University
Luciano Fiore: Northwestern University
Peng Gao: Northwestern University Feinberg School of Medicine
Lauren P. Diebold: Northwestern University, Feinberg School of Medicine
Gregory S. McElroy: Northwestern University, Feinberg School of Medicine
Ali Shilatifard: Northwestern University Feinberg School of Medicine
Navdeep S. Chandel: Northwestern University, Feinberg School of Medicine
Guillermo Oliver: Northwestern University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39672-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39672-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39672-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().