Abstract
Most regions of the CNS contain many subtypes of inhibitory interneurons with specialized roles in circuit function. In the mammalian retina, the ∼30 subtypes of inhibitory interneurons called amacrine cells (ACs) are generally divided into two groups: wide/medium-field GABAergic ACs and narrow-field glycinergic ACs, which mediate lateral and vertical interactions, respectively, within the inner plexiform layer. We used expression profiling and mouse transgenic lines to identify and characterize two closely related narrow-field AC subtypes. Both arise postnatally and one is neither glycinergic nor GABAergic (nGnG). Two transcription factors selectively expressed by these subtypes, Neurod6 and special AT-rich-sequence-binding protein 2 (Satb2), regulate a postmitotic cell fate choice between these subtypes. Satb2 induces Neurod6, which persists in nGnG ACs and promotes their fate but is downregulated in the related glycinergic AC subtype. Our results support the view that cell fate decisions made in progenitors and their progeny act together to diversify ACs.
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 / classification*
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Amacrine Cells / metabolism*
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Animals
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Animals, Newborn
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Basic Helix-Loop-Helix Transcription Factors / deficiency
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Bromodeoxyuridine / metabolism
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Electroporation / methods
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Embryo, Mammalian
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Glutamate Decarboxylase / metabolism
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Glycine / metabolism
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Glycine Plasma Membrane Transport Proteins / metabolism
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In Vitro Techniques
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Luminescent Proteins / metabolism
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Macaca
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Matrix Attachment Region Binding Proteins / metabolism
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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 / metabolism*
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Retina / cytology*
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Retina / embryology
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Retina / growth & development
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Shiga Toxin 1 / metabolism
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Transcription Factors / metabolism
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gamma-Aminobutyric Acid / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Ebf2 protein, mouse
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Glycine Plasma Membrane Transport Proteins
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Luminescent Proteins
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Matrix Attachment Region Binding Proteins
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Nerve Tissue Proteins
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Neurod6 protein, mouse
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SATB2 protein, mouse
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Shiga Toxin 1
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Slc6a9 protein, mouse
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Transcription Factors
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gamma-Aminobutyric Acid
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Glutamate Decarboxylase
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glutamate decarboxylase 1
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glutamate decarboxylase 2
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Bromodeoxyuridine
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Glycine