Lhx9 Is Required for the Development of Retinal Nitric Oxide-Synthesizing Amacrine Cell Subtype

• Published in: Molecular neurobiology 2018-04, Vol.55 (4), p.2922-2933
• Main Authors: Balasubramanian, Revathi, Bui, Andrew, Dong, Xuhui, Gan, Lin
• Format: Article
• Language: English
• Subjects: Amacrine cells; Amacrine Cells - cytology; Amacrine Cells - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Lineage; Dendrites - metabolism; GABAergic Neurons - metabolism; Gene regulation; Glutamate Decarboxylase - metabolism; Homeobox; Interneurons; LIM-Homeodomain Proteins - metabolism; Mice; Neurobiology; Neurology; Neurosciences; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type I - metabolism; Nitric-oxide synthase; Phenotype; Retina; Retina - cytology; Retinal Neurons - metabolism; Transcription Factors - metabolism; γ-Aminobutyric acid
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0554-y

Amacrine cells are the most diverse group of retinal neurons. Various subtypes of amacrine interneurons mediate a vast majority of image forming and non-image forming visual functions. The transcriptional regulation governing the development of individual amacrine cell subtypes is not well understood. One such amacrine cell subtype comprises neuronal nitric oxide synthase (nNOS/bNOS/NOS1)-expressing amacrine cells (NOACs) that regulate the release of nitric oxide (NO), a neurotransmitter with physiological and clinical implications in the retina. We have identified the LIM-homeodomain transcription factor LHX9 to be necessary for the genesis of NOACs. During retinal development, NOACs express Lhx9 , and Lhx9- null retinas lack NOACs. Lhx9 -null retinas also display aberrations in dendritic stratification at the inner plexiform layer. Our cell lineage-tracing studies show that Lhx9 -expressing cells give rise to both the GAD65 and GAD67 expressing sub-populations of GABAergic amacrine cells. As development proceeds, Lhx9 is downregulated in the GAD65 sub-population of GABAergic cells and is largely restricted to the GAD67 sub-population of amacrine cells that NOACs are a part of. Taken together, we have uncovered Lhx9 as a new molecular marker that defines a subset of amacrine cells and show that it is necessary for the development of the NOAC subtype of amacrine cells.