AI Article Synopsis

  • * The Notch signaling pathway acts as a suppressor of Atoh7 expression, regulating its transcription during retinal development.
  • * Research has identified key binding sites for Rbpj protein within Atoh7’s regulatory region, revealing that Rbpj represses Atoh7 transcription through both Notch-dependent and independent mechanisms.

Article Abstract

In vertebrate retinal progenitor cells, the proneural factor Atoh7 exhibits a dynamic tissue and cellular expression pattern. Although the resulting Atoh7 retinal lineage contains all seven major cell types, only retinal ganglion cells require Atoh7 for proper differentiation. Such specificity necessitates complex regulation of Atoh7 transcription during retina development. The Notch signaling pathway is an evolutionarily conserved suppressor of proneural bHLH factor expression. Previous in vivo mouse genetic studies established the cell autonomous suppression of Atoh7 transcription by Notch1, Rbpj and Hes1. Here we identify four CSL binding sites within the Atoh7 proximal regulatory region and demonstrate Rbpj protein interaction at these sequences by in vitro electromobility shift, calorimetry and luciferase assays and, in vivo via colocalization and chromatin immunoprecipitation. We found that Rbpj simultaneously represses Atoh7 transcription using both Notch-dependent and -independent pathways.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033939PMC
http://dx.doi.org/10.1038/s41598-018-28420-yDOI Listing

Publication Analysis

Top Keywords

atoh7 transcription
16
atoh7
8
regulation atoh7
8
rbpj
4
rbpj direct
4
direct regulation
4
transcription
4
transcription embryonic
4
embryonic mouse
4
mouse retina
4

Similar Publications

Article Synopsis
  • The study focuses on adult zebrafish that are blind due to mutations in the atoh7 gene, which prevents the formation of retinal ganglion cells (RGCs).
  • Researchers characterized the physical and behavioral traits of these mutants using various scientific techniques, noting distinct characteristics like dark pigmentation and reduced body size.
  • The findings highlight that these adult zebrafish serve as a valuable model for studying conditions like glaucoma and optic nerve aplasia by providing insights into retinal and tectal structure.
View Article and Find Full Text PDF

How tissue-specific progenitor cells generate adult tissues is a puzzle in organogenesis. Using single-cell RNA sequencing of control and Six3 and Six6 compound-mutant mouse embryonic eyecups, we demonstrated that these two closely related transcription factors jointly control diverse target genes in multiple cell populations over the developmental trajectories of mouse embryonic retinal progenitor cells. In the Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) graph of control retinas, naïve retinal progenitor cells had two major trajectories leading to ciliary margin cells and retinal neurons, respectively.

View Article and Find Full Text PDF

Multi-dataset identification of innovative feature genes and molecular mechanisms in keratoconus.

J Cell Mol Med

September 2024

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Article Synopsis
  • This study focused on identifying specific genes related to keratoconus (KC) and exploring its molecular mechanisms using various bioinformatics tools and databases.
  • It found 593 upregulated and 473 downregulated genes, highlighting ATOH7, MYRF, and others as key feature genes linked to immune cell infiltration in KC.
  • The research also identified potential therapeutic drugs like Entinostat and GSK-3-inhibitor-II, while confirming significant differences in gene expression levels related to KC.
View Article and Find Full Text PDF
Article Synopsis
  • Adeno-associated virus (AAV) can effectively deliver genes to retinal ganglion cells (RGCs), but there's a limitation due to packaging size and cell selectivity of the therapeutic genes.
  • This study evaluates the effectiveness of various RGC-selective promoters, including gamma-synuclein (SNCG) and neurofilament heavy chain (NEFH), alongside parts of the atonal bHLH transcription factor 7 (ATOH7) enhancer.
  • Results indicate that both SNCG and NEFH promoters are similarly effective for gene delivery and enhancing RGC survival, but the NEFH promoter has the advantage of a smaller size for packaging, making it more suitable for delivering larger genes in future applications.
View Article and Find Full Text PDF

The proneural transcription factor atonal basic helix-loop-helix transcription factor 7 () is expressed in early progenitors in the developing neuroretina. In vertebrates, this is crucial for the development of retinal ganglion cells (RGCs), as mutant animals show an almost complete absence of RGCs, underdeveloped optic nerves, and aberrations in retinal vessel development. Human mutations are rare and result in autosomal recessive optic nerve hypoplasia (ONH) or severe vascular changes, diagnosed as autosomal recessive persistent hyperplasia of the primary vitreous (PHPVAR).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: