Zbtb20 modulates the sequential generation of neuronal layers in developing cortex.
During corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Transcription factor Zbtb20 has been shown to play a role for hippocampal development but whether it is implicated in mammalian neocortical morphogenesis remains unknown.



Here, we report that during embyogenesis transcription factor Zbtb20 has a dynamic spatio-temporal expression pattern in mitotic cortical progenitors through which it modulates the sequential generation of cortical neuronal layer identities. Zbtb20 knock out mice exhibited enhanced populations of early born L6-L4 neuronal subtypes and a dramatic reduction of the late born L3/L2 neurons. This defect was due to a temporal misbalance in the production of earlier versus later born neurons, leading to a progressive diminishing of the progenitor pool for the generation of L3-L2 neurons. Zbtb20 implements these temporal effects in part by binding to promoter of the orphan nuclear receptor CoupTF1/Nr2f1. In addition to its effects exerted in cortical progenitors, the postmitotic expression of Zbtb20 in L3/L2 neurons starting at birth may contribute to their proper differentiation and migration.



Our findings reveal Zbtb20 as a novel temporal regulator for the generation of layer-specific neuronal identities.
Molecular Developmental Neurobiology Laboratory, Max Planck Institute of Biophysical Chemistry, Am Fassberg, 37077, Gottingen, Germany. anton.tonchev@mu-varna.bg.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075, Göttingen, Germany. anton.tonchev@mu-varna.bg.|Department of Anatomy, Histology and Embryology, Medical University-Varna, Varna, Bulgaria. anton.tonchev@mu-varna.bg.
Anton B
AB
Tonchev
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075, Göttingen, Germany.|Molecular Neurobiology Group, Institute of Neuroanatomy, University of Goettingen Medical Center, Goettingen, Germany.
Tran Cong
TC
Tuoc
Molecular Developmental Neurobiology Laboratory, Max Planck Institute of Biophysical Chemistry, Am Fassberg, 37077, Gottingen, Germany.
Eva H
EH
Rosenthal
University Nice Sophia Antipolis, iBV, UMR 7277, F-06108, Nice, France.|Inserm, iBV, U1091, F-06108, Nice, France.
Michèle
M
Studer
Molecular Developmental Neurobiology Laboratory, Max Planck Institute of Biophysical Chemistry, Am Fassberg, 37077, Gottingen, Germany. astoyko@gwdg.de.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075, Göttingen, Germany. astoyko@gwdg.de.|Department of Anatomy, Histology and Embryology, Medical University-Varna, Varna, Bulgaria. astoyko@gwdg.de.
Anastassia
A
Stoykova
D000818:Animals; D002453:Cell Cycle; D019070:Cell Lineage; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D008822:Mice, Transgenic; D008954:Models, Biological; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*
D014157:Transcription Factors; C520426:Zbtb20 protein, mouse
Development; Neocortex; Temporal identity; Transcription factor; Zbtb20