title: Ascl1 and Helt act combinatorially to specify thalamic neuronal identity by repressing Dlxs activation.
abstract: The mammalian thalamus is an essential diencephalic derivative that plays unique roles in processing and relaying sensory and motor information to and from the cerebral cortex. The profile of transcription factors and lineage tracing experiments revealed a spatiotemporal relationship between diencephalic progenitor domains and discrete differentiated neurons contributing to thalamic nuclei. However, the precise molecular mechanisms by which heterogeneous thalamic neurons become specified and assemble into distinct thalamic nuclei are still poorly understood. Here, we show that a combinatorial interaction between the bHLH transcription factors Ascl1 and Helt is required for acquiring thalamic progenitor identity. Surprisingly, in the combined absence of Ascl1 and Helt, rostral thalamic progenitors (TH-R) adopt a molecular profile of a more rostral diencephalic derivative, the prethalamus. Furthermore, we show that the prethalamic factors Dlxs upregulated by Ascl1/Helt deficiency play unique roles in regulating thalamic progenitor specification, and that derepression of Dlx2 and Dlx5 suppress generation of TH-R neurons. Taken together, our results suggest a model whereby the combined activity of two distinct bHLH factors plays a key role in the development of discrete classes of thalamic interneurons.
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Hobeom
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Bumwhee
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Dohoon
authors.initials: D
authors.lastname: Pyun
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.
authors.forename: Jordi
authors.initials: J
authors.lastname: Guimera
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Youngsook
authors.initials: Y
authors.lastname: Son
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea.
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, D-85764 Neuherberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Yongin-si 446-701, Republic of Korea. Electronic address: yongsu@khu.ac.kr.
authors.forename: Yongsu
authors.initials: Y
authors.lastname: Jeong
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D019070:Cell Lineage; D050989:GATA2 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050989:GATA2 Transcription Factor; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; C494712:Gata2 protein, mouse; C487897:Helt protein, mouse
keywords: Ascl1; Dlx; Helt; Thalamus