Independent control of neurogenesis and dorsoventral patterning by NKX2-2.
Overview
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York 10032, USA
- Department of Neuroscience, Columbia University Irving Medical Center, New York, New York 10032, USA
- Department of Neurology, Columbia University Irving Medical Center, New York, New York 10032, USA
- Center for Motor Neuron Biology and Disease, Columbia University Irving Medical Center, New York, New York 10032, USA
- Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, New York 10032, USA
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA
Abstract
Human neurogenesis is disproportionately protracted, lasting >10 times longer than in mice, allowing neural progenitors to undergo more rounds of self-renewing cell divisions and generate larger neuronal populations. In the human spinal cord, expansion of the motor neuron lineage is achieved through a newly evolved progenitor domain called the ventral motor neuron progenitor (vpMN) that delays and expands motor neurogenesis. This behavior of vpMNs is controlled by transcription factor NKX2-2, which in vpMNs is coexpressed with classical motor neuron progenitor (pMN) marker OLIG2. In this study, we sought to determine the molecular basis of NKX2-2-mediated extension and expansion of motor neurogenesis. We found that, unlike in mice or chicks, NKX2-2 in the human spinal cord does not repress dorsoventral patterning genes like OLIG2. However, it retains its ability to repress NEUROG2, a proneural gene that promotes exit from the cell cycle and motor neurogenesis. Interestingly, we found that ectopic expression of Tinman mutant Nkx2-2 in mouse pMNs phenocopies human vpMNs, repressing Neurog2 but not Olig2, resulting in delayed motor neurogenesis. Thus, our studies reveal that the classical patterning function of NKX2-2 that depends on its Tinman repressive domain is dissociated from NKX2-2's ability to repress NEUROG2 to control the onset and duration of motor neurogenesis in human ventral motor neuron progenitors.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Datasets cited
- geo:GSE310451, at NCBI GEO; found in “Data availability”
Data availability
ChIP-seq and RNA-seq data sets produced in this study are available in the Gene Expression Omnibus under accession number GSE310451 (https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 4 keywords, 17 MeSH terms, 6 funders, 43 references, 3 RRIDs.
Cite
This paper
Jang, S., Abarinov, E. V., Dobkin, J. A., Hurley, E. C., Closser, M., Sussel, L., & Wichterle, H. (2026). Independent control of neurogenesis and dorsoventral patterning by NKX2-2. Genes & development, 40(5-6), 384-395. https://
BibTeX
@article{jang2026indepen
author = {Jang, Sumin and Abarinov, Elena V and Dobkin, Julie A and Hurley, Erica C and Closser, Michael and Sussel, Lori and Wichterle, Hynek},
title = {{Independent control of neurogenesis and dorsoventral patterning by NKX2-2}},
journal = {Genes \& development},
year = {2026},
month = mar,
volume = {40},
number = {5-6},
pages = {384--395},
publisher = {Cold Spring Harbor Laboratory Press},
issn = {0890-9369},
doi = {10.1101/
url = {https://
pmid = {41526180},
pmcid = {PMC12951754}
}
RIS
TY - JOUR
AU - Jang, Sumin
AU - Abarinov, Elena V
AU - Dobkin, Julie A
AU - Hurley, Erica C
AU - Closser, Michael
AU - Sussel, Lori
AU - Wichterle, Hynek
TI - Independent control of neurogenesis and dorsoventral patterning by NKX2-2
T2 - Genes & development
J2 - Genes Dev
PY - 2026
DA - 2026/
VL - 40
IS - 5-6
SP - 384
EP - 395
SN - 0890-9369
PB - Cold Spring Harbor Laboratory Press
DO - 10.1101/
UR - https://
LA - en
ER -
CSL-JSON
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"author": [
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"family": "Jang",
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},
{
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"family": "Hurley",
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"issue": "5-6",
"page": "384-395",
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"URL": "https://
"language": "en",
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