Related Experiment Video
Updated: Jun 25, 2025
Organotypic Retinal Explant Cultures from Macaque Monkey
Published on: August 24, 2022
Mutant kri1l causes abnormal retinal development via cell cycle arrest and apoptosis induction
Rong Zhang1,2,3, Jiajun Sun1,2, Yabin Xie2,4
1Department of Basic Medicine and Forensic Medicine, Baotou Medical College, Inner Mongolia, Baotou, China.
Abstract:
Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.
Insights
The kri1l gene is crucial for retinal development. Mutations disrupt eye structure, leading to cell loss and potential vision impairment, highlighting its role in preventing diseases like diabetic retinopathy.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Ribosome damage and protein biosynthesis imbalance are linked to human diseases, including diabetic retinopathy (DR).
- The kri1l gene's role in retinal development was previously unclear.
Purpose of the Study:
- To investigate the function of the kri1l gene in retinal development.
- To understand the molecular mechanisms underlying retinal abnormalities in kri1l mutants.
Main Methods:
- Analysis of kri1l gene function in zebrafish or other model organisms.
- Histological examination of retinal structure in wild-type and kri1l mutant embryos.
- Assessment of cell proliferation, apoptosis, and DNA damage markers (e.g., γ-H2AX).
- Gene expression analysis of retinal development-related genes, including opsins.
Main Results:
- kri1l mutants exhibit disrupted retinal structure, resulting in small eyes with blurred and narrowed retinal cell layers.
- Photoreceptor and Müller glia cells are significantly reduced or absent in kri1l mutants.
- Abnormalities initiate post-fertilization, with defective cell differentiation, increased proliferation, and enhanced apoptosis.
- Upregulation of γ-H2AX indicates DNA damage, leading to cell cycle arrest and apoptosis.
- Reduced expression of opsin and key retinal genes was observed in kri1l mutants.
Conclusions:
- The kri1l gene is essential for normal retinal development and structure.
- Defects in kri1l lead to severe retinal abnormalities, including cell loss and impaired differentiation.
- Understanding kri1l's function provides insights into eye diseases potentially linked to ribosomal or protein biosynthesis dysfunction.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:34Inhibition of Cdk Activity
01:16In-vitro Mutagenesis
02:23Abnormal Proliferation
01:23Negative Regulator Molecules