Committed neuronal precursors confer astrocytic potential on residual neural precursor cells.
During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor I, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes.
Namihira
Masakazu
M
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
Kohyama
Jun
J
Semi
Katsunori
K
Sanosaka
Tsukasa
T
Deneen
Benjamin
B
Taga
Tetsuya
T
Nakashima
Kinichi
K
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001381:Azepines / Q000494:pharmacology; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008954:Models, Biological; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013447:Sulfites / Q000737:chemistry; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D001381:Azepines; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; D051880:Receptors, Notch; D013447:Sulfites; D014157:Transcription Factors; D000409:Alanine; C042345:hydrogen sulfite