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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
PubMed

Insights

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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