Abstract
Through transcriptional regulations, the BarH family of homeodomain proteins play essential roles in cell fate specification, cell differentiation, migration, and survival. Barhl2, a member of the Barh gene family, is expressed in retinal ganglion cells (RGCs), amacrine cells (ACs), and horizontal cells. Here, to investigate the role of Barhl2 in retinal development, Barhl2-deficient mice were generated. Analysis of AC subtypes in Barhl2-deficient retinas suggests that Barhl2 plays a critical role in AC subtype determination. A significant reduction of glycinergic and GABAergic ACs with a substantial increase in the number of cholinergic ACs was observed in Barhl2-null retinas. Barhl2 is also critical for the development of a normal complement of RGCs. Barhl2 deficiency resulted in a 35% increase in RGCs undergoing apoptosis during development. Genetic analysis revealed that Barhl2 functions downstream of the Atoh7-Pou4f3 regulatory pathway and regulates the maturation and/or survival of RGCs. Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amacrine Cells / physiology*
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Animals
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Animals, Newborn
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Apoptosis / genetics
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / physiology*
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Embryo, Mammalian
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology
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Glutamate Decarboxylase / genetics
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Glutamate Decarboxylase / metabolism
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Glycine Plasma Membrane Transport Proteins / genetics
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Glycine Plasma Membrane Transport Proteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Homeodomain Proteins / physiology*
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LIM-Homeodomain Proteins
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / physiology*
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PAX6 Transcription Factor
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Paired Box Transcription Factors / genetics
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Paired Box Transcription Factors / metabolism
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Photic Stimulation / methods
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Retina* / cytology
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Retina* / embryology
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Retina* / growth & development
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Retinal Ganglion Cells / physiology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Transcription Factor Brn-3A / genetics
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Transcription Factor Brn-3A / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Visual Perception / genetics
Substances
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Barhl2 protein, mouse
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Eye Proteins
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Glycine Plasma Membrane Transport Proteins
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Nerve Tissue Proteins
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Pou4f1 protein, mouse
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Repressor Proteins
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Slc6a9 protein, mouse
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Transcription Factor Brn-3A
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Transcription Factors
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Vsx2 protein, mouse
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insulin gene enhancer binding protein Isl-1
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Caspase 3
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Glutamate Decarboxylase
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glutamate decarboxylase 2