Differential <i>Hes1</i> activation defines neural stem cell lineage commitment and niche maintenance in embryonic and adult mouse cortex
Abstract
Mode of Hes1 activation and its differential expression are crucial for the maintenance of neural stem cells/progenitor cells (NSCs/NPCs) in the embryonic cortex. This differential mode of Hes1 activation has been translated into a heterogeneous population of NSCs comprising Notch-independent Hes1- expressing (NIHes1) NSCs and Notch-dependent Hes1- expressing (NDHes1) radial glial cells (RGCs). Using single-cell transcriptomics and a Nestin-CreERT2;NIHes1 fl/fl conditional knock-out mouse model, we have characterized the NIHes1 NSCs. Our analyses show that NIHes1 NSCs are the ancestral precursor NSCs that generate RGCs and intermediate progenitor cells during development. Loss of NIHes1 expression significantly alters the NSC niche, leading to increased gliogenesis and aberrant migration of projection neurons. NIHes1 NSCs are set aside at embryonic stages as adult neural stem cells and are maintained by NIHes1 expression even at adult stage. Our findings suggest that NIHes1 NSCs are functionally distinct Hes1 -expressing NSCs, which are critical for establishing both embryonic and adult NSC niches, thereby contributing to the overall cortical development.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Paul Ann Riya
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Rahul Jose
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Vadakkath Meera
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Budhaditya Basu
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Suresh Surya
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Ramankunju Aryasree
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Nair Pradeep Jyothi
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Surendran Parvathy
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Sivadasan Bindu Dhanesh
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology
Rajendran Sanalkumar
Institut universitaire de pathologie, Centre hospitalier universitaire vaudois-Lausanne University Hospital
Viviane Praz
Institut universitaire de pathologie, Centre hospitalier universitaire vaudois-Lausanne University Hospital
Nicolo Riggi
Institut universitaire de pathologie, Centre hospitalier universitaire vaudois-Lausanne University Hospital
Jackson James
Neuro Stem Cell Biology Laboratory, Neurobiology Division, Biotechnology Research and Innovation Council-Rajiv Gandhi Centre for Biotechnology