title: Satb2 Regulates the Differentiation of Both Callosal and Subcerebral Projection Neurons in the Developing Cerebral Cortex.
abstract: The chromatin-remodeling protein Satb2 plays a role in the generation of distinct subtypes of neocortical pyramidal neurons. Previous studies have shown that Satb2 is required for normal development of callosal projection neurons (CPNs), which fail to extend axons callosally in the absence of Satb2 and instead project subcortically. Here we conditionally delete Satb2 from the developing neocortex and find that neurons in the upper layers adopt some electrophysiological properties characteristic of deep layer neurons, but projections from the superficial layers do not contribute to the aberrant subcortical projections seen in Satb2 mutants. Instead, axons from deep layer CPNs descend subcortically in the absence of Satb2. These data demonstrate distinct developmental roles of Satb2 in regulating the fates of upper and deep layer neurons. Unexpectedly, Satb2 mutant brains also display changes in gene expression by subcerebral projection neurons (SCPNs), accompanied by a failure of corticospinal tract (CST) formation. Altering the timing of Satb2 ablation reveals that SCPNs require an early expression of Satb2 for differentiation and extension of the CST, suggesting that early transient expression of Satb2 in these cells plays an essential role in development. Collectively these data show that Satb2 is required by both CPNs and SCPNs for proper differentiation and axon pathfinding.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Dino P
authors.initials: DP
authors.lastname: Leone
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Heavner
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Ferenczi
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany.
authors.forename: Gergana
authors.initials: G
authors.lastname: Dobreva
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Susan K
authors.initials: SK
authors.lastname: McConnell
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D003337:Corpus Callosum / Q000196:embryology* / Q000378:metabolism; D005260:Female; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D013003:Somatosensory Cortex / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors
keywords: Ctip2; Fezf2; callosal projection neuron; corticospinal tract; development; pyramidal neuron; specification