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Ndr kinases regulate retinal interneuron proliferation and homeostasis.
Hélène Léger1, Evelyn Santana2, N Adrian Leu3
1Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, United States.
Scientific Reports
|August 24, 2018
Summary
Ndr kinases regulate retinal cell function. Deleting Ndr kinases in mice caused abnormal amacrine cell proliferation and decreased synaptic organization, impacting neuronal health.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Ndr2/Stk38l, a kinase in the Hippo pathway, is linked to canine retinal degeneration.
- The roles of Ndr2 and its paralog Ndr1/Stk38 in retinal development and function are not fully understood.
Purpose of the Study:
- To investigate the retinal functions of Ndr1 and Ndr2 kinases.
- To understand the molecular mechanisms underlying Ndr kinase-mediated retinal cell regulation.
Main Methods:
- Generation of Ndr1 and Ndr2 single knockout mouse models.
- Analysis of retinal lamination and cell populations (Pax6, GABAergic, HuD).
- Retinal transcriptome analysis and assessment of Ndr substrate Aak1 levels.
Main Results:
- Ndr deletion in mice did not affect overall retinal lamination.
- Ndr deletion led to proliferation of Pax6-positive amacrine cells and reduced numbers of specific amacrine cell types.
- Transcriptome analysis revealed increased neuronal stress and decreased synaptic organization gene expression in Ndr-deleted retinas.
- Ndr deletion significantly reduced levels of the Ndr substrate Aak1, a regulator of vesicle trafficking.
Conclusions:
- Ndr kinases are crucial for regulating amacrine and photoreceptor cell populations in the retina.
- Ndr kinases appear to inhibit proliferation in terminally differentiated retinal cells.
- Ndr kinases modulate interneuron synapse function, potentially through the Aak1 pathway.
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