title: Fezf2 expression in layer 5 projection neurons of mature mouse motor cortex.
abstract: The mature cerebral cortex contains a wide diversity of neuron phenotypes. This diversity is specified during development by neuron-specific expression of key transcription factors, some of which are retained for the life of the animal. One of these key developmental transcription factors that is also retained in the adult is Fezf2, but the neuron types expressing it in the mature cortex are unknown. With a validated Fezf2-Gfp reporter mouse, whole-cell electrophysiology with morphology reconstruction, cluster analysis, in vivo retrograde labeling, and immunohistochemistry, we identify a heterogeneous population of Fezf2(+) neurons in both layer 5A and layer 5B of the mature motor cortex. Functional electrophysiology identified two distinct subtypes of Fezf2(+) neurons that resembled pyramidal tract projection neurons (PT-PNs) and intratelencephalic projection neurons (IT-PNs). Retrograde labeling confirmed the former type to include corticospinal projection neurons (CSpPNs) and corticothalamic projection neurons (CThPNs), whereas the latter type included crossed corticostriatal projection neurons (cCStrPNs) and crossed-corticocortical projection neurons (cCCPNs). The two Fezf2(+) subtypes expressed either CTIP2 or SATB2 to distinguish their physiological identity and confirmed that specific expression combinations of key transcription factors persist in the mature motor cortex. Our findings indicate a wider role for Fezf2 within gene expression networks that underpin the diversity of layer 5 cortical projection neurons.
authors.affiliation: Department of Physiology, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Malinda L S
authors.initials: ML
authors.lastname: Tantirigama
authors.affiliation: Department of Physiology, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Manfred J
authors.initials: MJ
authors.lastname: Oswald
authors.affiliation: Department of Biochemistry, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Clare
authors.affiliation: Department of Biochemistry, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Hollie E
authors.initials: HE
authors.lastname: Wicky
authors.affiliation: Department of Biochemistry, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Day
authors.affiliation: Department of Biochemistry, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Hughes
authors.affiliation: Department of Physiology, Brain Health Research Centre, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand, 9054.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Empson
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011712:Pyramidal Tracts / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C412364:Zfp312 protein, mouse; D049452:Green Fluorescent Proteins
keywords: Fezf2; IT type; PT type; RRID:AB_10561696; RRID:AB_2064130; RRID:AB_882455; RRID:nif-0000-30467; cortex; electrophysiology; layer 5; transcription factors