Evidence map›Paper›PMID 41650955›Full record

ArticleDevelopmental cell2026

Hypoxia-inducible factor signaling regulates embryonic interneuron development, GRIN2B expression and adult cortical function.

I-Ling Lu, Mengyi Song, Cinthia Rangel-Sandoval, Juan Moriano Palacios, JaeYeon Kim, Eric J Huang, Arturo Alvarez-Buylla, Arnold Kriegstein, Mercedes F Paredes, David H Rowitch

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

I-Ling LuThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Pediatrics, Division of Neonatology, UCSF, San Francisco, CA 94158, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA.
Mengyi SongThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA.
Cinthia Rangel-SandovalDepartments of Pediatrics and Neurosurgery, Cedars-Sinai Guerin Children's, Los Angeles, CA 900485, USA.
Juan Moriano PalaciosThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA.
JaeYeon KimThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA.
Eric J HuangDepartment of Pathology, UCSF, San Francisco, CA 94143, USA.
Arturo Alvarez-BuyllaThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurological Surgery, UCSF, San Francisco, CA 94143, USA.
Arnold KriegsteinThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA.
Mercedes F ParedesThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Neurology, UCSF, San Francisco, CA 94143, USA; Weill Institute for Neuroscience, UCSF, San Francisco, CA 94158, USA. Electronic address: mercedes.paredes@ucsf.edu.
David H RowitchThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Pediatrics, Division of Neonatology, UCSF, San Francisco, CA 94158, USA; Departments of Pediatrics and Neurosurgery, Cedars-Sinai Guerin Children's, Los Angeles, CA 900485, USA; Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: david.rowitch@cshs.org.

Funding

Regulation of Cellular Pathwaysin Human Brain DevelopmentP01NS083513 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PIAO, XIANHUA · 2014 to 2024
$12.6M
Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brainsU01MH130995 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Chongyuan Luo, Mercedes Paredes · 2022 to 2026
$4.4M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
Protracted Maturation of Cortical Inhibitory Neurons for the Complexity of Higher Cognitive AreasK99NS138587 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jaeyeon Kim · 2025 to 2026
$231k
NIH HHS S10 OD028511NIMH NIH HHS U01 MH130995NINDS NIH HHS K99 NS138587NINDS NIH HHS P01 NS083513
6 · The paper itself

Abstract

Although hypoxia-inducible factors (HIFs) are central regulators of cellular adaptation to oxygen and metabolic fluctuations in the mammalian brain, potential roles for HIF regulation during inhibitory neuron development are poorly understood. Here, we report that Nkx2.1-cre-driven conditional deletion of Hif1/2a in the medial ganglionic eminence (MGE) leads to reduced proliferation of Lhx6-positive interneuron precursors, whereas loss of von Hippel-Lindau (vHL), required for HIF degradation, drives increased precursor proliferation. Integrating single-cell transcriptomics, we identified HIF targets regulating proliferation and synaptogenesis. We also show that HIF1A directly activates glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), encoding glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) subunit 2B. In the adult HIF1 conditional knockout (cKO) cortex, we observed decreased numbers of parvalbumin (PV) interneurons and fewer GABAergic synapses and GRIN2B/Bassoon puncta on layer 2/3 excitatory neurons, resulting in attenuated long-term potentiation. These findings identify non-canonical roles for HIF signaling that are essential for PV interneuron production, GRIN2B expression, and cortical circuit maturation and function.

Indexed as

Basic Helix-Loop-Helix ProteinsCerebral CortexHypoxia-Inducible Factor 1, alpha SubunitInterneuronsReceptors, N-Methyl-D-AspartateAnimalsCell ProliferationEndothelial PAS Domain-Containing Protein 1GABAergic NeuronsGanglionic EminenceGene Expression Regulation, DevelopmentalLIM-Homeodomain ProteinsMiceMice, KnockoutNerve Tissue ProteinsNeurodevelopmentBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitLHX6 protein, mouseLIM-Homeodomain ProteinsNerve Tissue ProteinsNkx2-1 protein, mouseNR2B NMDA receptorParvalbuminsReceptors, N-Methyl-D-AspartateThyroid Nuclear Factor 1Transcription FactorsVHL protein, mouseVon Hippel-Lindau Tumor Suppressor Proteinembryonic brainGRIN2BHif1ahyperoxiahypoxia-inducible factorinterneuronLhx6Nkx2.1parvalbuminpreterm infant brain injury

Identifiers

PMID41650955
PMCPMC13390556

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.