TY - JOUR
T1 - Lhx9 Is Required for the Development of Retinal Nitric Oxide-Synthesizing Amacrine Cell Subtype
AU - Balasubramanian, Revathi
AU - Bui, Andrew
AU - Dong, Xuhui
AU - Gan, Lin
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - Amacrine cell subtype
KW - LIM-homeodomain transcription factor
KW - Retina
KW - Retinal lamination
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U2 - 10.1007/s12035-017-0554-y
DO - 10.1007/s12035-017-0554-y
M3 - Article
C2 - 28456934
AN - SCOPUS:85018257071
SN - 0893-7648
VL - 55
SP - 2922
EP - 2933
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 4
ER -