title: Prdm13 mediates the balance of inhibitory and excitatory neurons in somatosensory circuits.
abstract: Generating a balanced network of inhibitory and excitatory neurons during development requires precise transcriptional control. In the dorsal spinal cord, Ptf1a, a basic helix-loop-helix (bHLH) transcription activator, maintains this delicate balance by inducing homeodomain (HD) transcription factors such as Pax2 to specify the inhibitory lineage while suppressing HD factors such as Tlx1/3 that specify the excitatory lineage. We uncover the mechanism by which Ptf1a represses excitatory cell fate in the inhibitory lineage. We identify Prdm13 as a direct target of Ptf1a and reveal that Prdm13 actively represses excitatory cell fate by binding to regulatory sequences near the Tlx1 and Tlx3 genes to silence their expression. Prdm13 acts through multiple mechanisms, including interactions with the bHLH factor Ascl1, to repress Ascl1 activation of Tlx3. Thus, Prdm13 is a key component of a highly coordinated transcriptional network that determines the balance of inhibitory versus excitatory neurons in the dorsal spinal cord.
authors: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Joshua C
authors: JC
authors: Chang
authors: David M
authors: DM
authors: Meredith
authors: Paul R
authors: PR
authors: Mayer
authors: Mark D
authors: MD
authors: Borromeo
authors: Helen C
authors: HC
authors: Lai
authors: Yi-Hung
authors: YH
authors: Ou
authors: Jane E
authors: JE
authors: Johnson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000737:chemistry; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016335:Zinc Fingers
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; D034741:RNA, Small Interfering; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C497319:Pax2 protein, mouse; C487378:Tlx1 protein, mouse; C487377:Tlx3 protein, mouse; C062602:transcription factor PTF1
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