Regulation of thalamocortical patterning and synaptic maturation by NeuroD2.
During cortical development, both activity-dependent and genetically determined mechanisms are required to establish proper neuronal connectivity. While activity-dependent transcription may link the two processes, specific transcription factors that mediate such a process have not been identified. We identified the basic helix-loop-helix (bHLH) transcription factor Neurogenic Differentiation 2 (NeuroD2) in a screen for calcium-regulated transcription factors and report that it is required for the proper development of thalamocortical connections. In neuroD2 null mice, thalamocortical axon terminals fail to segregate in the somatosensory cortex, and the postsynaptic barrel organization is disrupted. Additionally, synaptic transmission is defective at thalamocortical synapses in neuroD2 null mice. Total excitatory synaptic currents are reduced in layer IV in the knockouts, and the relative contribution of AMPA and NMDA receptor-mediated currents to evoked responses is decreased. These observations indicate that NeuroD2 plays a critical role in regulating synaptic maturation and the patterning of thalamocortical connections.
Ince-Dunn
Gulayse
G
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hall
Benjamin J
BJ
Hu
Shu-Ching
SC
Ripley
Beth
B
Huganir
Richard L
RL
Olson
James M
JM
Tapscott
Stephen J
SJ
Ghosh
Anirvan
A
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D050882:CREB-Binding Protein / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D009434:Neural Pathways / Q000254:growth & development*; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000172:deficiency / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology / Q000254:growth & development*; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development*; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection / Q000379:methods; D014738:Vibrissae / Q000254:growth & development / Q000294:innervation
D015763:2-Amino-5-phosphonovalerate; D000596:Amino Acids; D051792:Basic Helix-Loop-Helix Proteins; D050882:CREB-Binding Protein; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D015500:Chloramphenicol O-Acetyltransferase; D004533:Egtazic Acid; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009414:Nerve Growth Factors; D009479:Neuropeptides; D009553:Nimodipine; D010751:Phosphopyruvate Hydratase; D011189:Potassium Chloride; D011724:Pyridazines; D011726:Pyridinium Compounds; D011810:Quinoxalines; D018091:Receptors, AMPA; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C098995:Neurod2 protein, mouse; C098463:dolaisoleucine; C076868:4-(4-dihexadecylaminostyryl)-N-methylpyridium; C056723:FG 9041; C049853:gabazine; C104722:glutamate receptor ionotropic, AMPA 2