title: Neurod6 expression defines new retinal amacrine cell subtypes and regulates their fate.
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.
authors: Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.
authors: Jeremy N
authors: JN
authors: Kay
authors: P Emanuela
authors: PE
authors: Voinescu
authors: Monica W
authors: MW
authors: Chu
authors: Joshua R
authors: JR
authors: Sanes
mesh_terms: D025042:Amacrine Cells / Q000145:classification* / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D008251:Macaca; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D022622:Shiga Toxin 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D005968:Glutamate Decarboxylase; D005998:Glycine; D050487:Glycine Plasma Membrane Transport Proteins; D008164:Luminescent Proteins; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; D022622:Shiga Toxin 1; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C489922:Ebf2 protein, mouse; C110701:Neurod6 protein, mouse; C501473:SATB2 protein, mouse; C493267:Slc6a9 protein, mouse; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2