Genome-wide target analysis of NEUROD2 provides new insights into regulation of cortical projection neuron migration and differentiation.
BACKGROUND
Cellular differentiation programs are controlled, to a large extent, by the combinatorial functioning of specific transcription factors. Cortical projection neurons constitute the major excitatory neuron population within the cortex and mediate long distance communication between the cortex and other brain regions. Our understanding of effector transcription factors and their downstream transcriptional programs that direct the differentiation process of cortical projection neurons is far from complete.


RESULTS
In this study, we carried out a ChIP-Seq (chromatin-immunoprecipitation and sequencing) analysis of NEUROD2, an effector transcription factor expressed in lineages of cortical projection neurons during the peak of cortical excitatory neurogenesis. Our results suggest that during cortical development NEUROD2 targets key genes that are required for Reelin signaling, a major pathway that regulates the migration of neurons from germinal zones to their final layers of residence within the cortex. We also find that NEUROD2 binds to a large set of genes with functions in layer-specific differentiation and in axonal pathfinding of cortical projection neurons.


CONCLUSIONS
Our analysis of in vivo NEUROD2 target genes offers mechanistic insight into signaling pathways that regulate neuronal migration and axon guidance and identifies genes that are likely to be required for proper cortical development.
Molecular Biology and Genetics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. ebayam@ku.edu.tr.
Efil
E
Bayam
Molecular Biology and Genetics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. ssahin@vetmed.wsu.edu.|Present Address: Neuroscience Department, Washington State University, Pullman, WA, 99164, USA. ssahin@vetmed.wsu.edu.
Gulcan Semra
GS
Sahin
Molecular Biology and Genetics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. gguzelsoy13@ku.edu.tr.
Gizem
G
Guzelsoy
Molecular Biology and Genetics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. gguner@ku.edu.tr.
Gokhan
G
Guner
Physics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. akabakcioglu@ku.edu.tr.
Alkan
A
Kabakcioglu
Molecular Biology and Genetics Department, Koç University, Rumeli Feneri Yolu, Istanbul, 34450, Turkey. gdunn@ku.edu.tr.
Gulayse
G
Ince-Dunn
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D000091042:Reelin Protein
D051792:Basic Helix-Loop-Helix Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; C098995:Neurod2 protein, mouse; C000717128:Reln protein, mouse