2024.01.12
The Transcription factor NF-YA is Crucial for Neural Progenitor Maintenance during Brain Development
J Biol Chem. 2024 Jan 8:105629. doi: 10.1016/j.jbc.2024.105629. Online ahead of print.
Yamanaka T1, Kurosawa M2, Yoshida A3, Shimogori T3, Hiyama A4, Maity SN5, Hattori N6, Matsui H7, Nukina N8.
1Department of Neuroscience of Disease, Brain Research Institute, Niigata University; Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science; Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science; Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine.
2Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine.
3Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science.
4Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science.
5Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, USA.
6Department of Neurology, Juntendo University Graduate School of Medicine.
7Department of Neuroscience of Disease, Brain Research Institute, Niigata University.
8Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science; Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science; Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine.
Abstract
In contrast to stage-specific transcription factors, the role of ubiquitous transcription factors in neuronal development remains a matter of scrutiny. Here, we demonstrated that a ubiquitous factor NF-Y is essential for neural progenitor maintenance during brain morphogenesis. Deletion of the NF-YA subunit in neural progenitors by using nestin-cre transgene in mice resulted in significant abnormalities in brain morphology, including a thinner cerebral cortex and loss of striatum during embryogenesis. Detailed analyses revealed a progressive decline in multiple neural progenitors in the cerebral cortex and ganglionic eminences, accompanied by induced apoptotic cell death and reduced cell proliferation. In neural progenitors, the NF-YA short isoform lacking exon 3 is dominant and co-expressed with cell cycle genes. ChIP-seq analysis from the cortex during early corticogenesis revealed preferential binding of NF-Y to the cell cycle genes, some of which were confirmed to be downregulated following NF-YA deletion. Notably, the NF-YA short isoform disappears and is replaced by its long isoform during neuronal differentiation. Forced expression of the NF-YA long isoform in neural progenitors resulted in a significant decline in neuronal count, possibly due to the suppression of cell proliferation. Collectively, we elucidated a critical role of the NF-YA short isoform in maintaining neural progenitors, possibly by regulating cell proliferation and apoptosis. Moreover, we identified an isoform switch in NF-YA within the neuronal lineage in vivo, which may explain the stage-specific role of NF-Y during neuronal development.
*Reprinted under the terms of the Creative Commons Attribution License (CC BY).
