Journal
CELL REPORTS
Volume 31, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.03.085
Keywords
-
Categories
Funding
- Strategic Priority Research Program'' of the Chinese Academy of Sciences [XDA16020501, XDA16020404]
- National Key Basic Research and Development Program of China [2018YFA0800100, 2018YFA0108000, 2018YFA0107200, 2017YFA0102700, 2015CB964500, 2014CB964804]
- National Natural Science Foundation of China [31671508, 31661143042, 91519314, 31630043, 31571513, 31430058, 31900454]
Ask authors/readers for more resources
Recent studies have revealed an essential role for embryonic cortical development in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the genetic basis and underlying mechanisms remain unclear. Here, we generate mutant human embryonic stem cell lines (Mut hESCs) carrying an NR2F1-R112K mutation that has been identified in a patient with ASD features and investigate their neurodevelopmental alterations. Mut hESCs overproduce ventral telencephalic neuron progenitors (ventral NPCs) and underproduce dorsal NPCs, causing the imbalance of excitatory/inhibitory neurons. These alterations can be mainly attributed to the aberrantly activated Hedgehog signaling pathway. Moreover, the corresponding Nr2f1 point-mutant mice display a similar excitatory/inhibitory neuron imbalance and abnormal behaviors. Antagonizing the increased inhibitory synaptic transmission partially alleviates their behavioral deficits. Together, our results suggest that the NR2F1 -dependent imbalance of excitatory/inhibitory neuron differentiation caused by the activated Hedgehog pathway is one precursor of neurodevelopmental disorders and may enlighten the therapeutic approaches.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available