title: Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons.
abstract: Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties.
  
  
  CONCLUSIONS
  Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons.
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, Goichi.Miyoshi@gmail.com fisheg01@nyumc.org.
authors.forename: Goichi
authors.identifier: http://orcid.org/0000-0002-1872-6278
authors.initials: G
authors.lastname: Miyoshi
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016.
authors.forename: Allison
authors.initials: A
authors.lastname: Young
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016.
authors.forename: Timothy
authors.initials: T
authors.lastname: Petros
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016.
authors.forename: Theofanis
authors.initials: T
authors.lastname: Karayannis
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016.
authors.forename: Melissa
authors.initials: M
authors.lastname: McKenzie Chang
authors.affiliation: Department of Genetics & Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavado
authors.affiliation: Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Iwano
authors.affiliation: Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and.
authors.forename: Miho
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors.forename: Z Josh
authors.initials: ZJ
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and.
authors.forename: Nathaniel
authors.identifier: http://orcid.org/0000-0002-8874-8704
authors.initials: N
authors.lastname: Heintz
authors.affiliation: Department of Genetics & Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Oliver
authors.affiliation: Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzaki
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Machold
authors.affiliation: Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, Goichi.Miyoshi@gmail.com fisheg01@nyumc.org.
authors.forename: Gord
authors.initials: G
authors.lastname: Fishell
mesh_terms: D000818:Animals; D015415:Biomarkers; D064032:Calbindin 2 / Q000032:analysis; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D019070:Cell Lineage; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D007395:Interneurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D015415:Biomarkers; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D014660:Vasoactive Intestinal Peptide; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: RELN; VIP; bipolar; mouse genetics; neurogliaform; transcription