Evidence map›Paper›PMID 41791387›Full record

ArticleStem cell reports2026

Delayed forebrain excitatory and inhibitory neurogenesis in STRADA-related megalencephaly via mTOR hyperactivity.

Tong Pan, Grace Lin, Xuan Li, Debora VanHeyningen, John C Walker, Sahej Kohli, Aiswarya Saravanan, Amrita Kondur, Daniel C Jaklic, Saul Pantoja-Gutierrez and 6 more

Abstract read
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In one paragraph

Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Tong PanDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address: topa@umich.edu.
Grace LinDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Xuan LiLaboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Debora VanHeyningenDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
John C WalkerDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Sahej KohliDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Aiswarya SaravananDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Amrita KondurDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Daniel C JaklicDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Saul Pantoja-GutierrezDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Shivanshi VaidDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Julie SturzaDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.
Ken InokiLife Sciences Institute, University of Michigan, Ann Arbor, MI, USA; Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Tomozumi ImamichiLaboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Weizhong ChangLaboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Louis T DangDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address: louisdan@med.umich.edu.

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Elucidating pathogenic mechanisms in STRADA-related brain malformation and epilepsyR01NS127829 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Louis Tuong Chinh Dang · 2022 to 2026
$2.1M
NCI NIH HHS P30 CA046592NINDS NIH HHS R01 NS127829
6 · The paper itself

Abstract

Biallelic pathogenic variants in STRADA (STE20-related adaptor alpha), an upstream regulator of the mechanistic target of rapamycin (mTOR) pathway, result in megalencephaly, drug-resistant epilepsy, and severe intellectual disability. This study explores how mTOR pathway hyperactivity alters cell fate specification in dorsal and ventral forebrain development using STRADA knockout human stem cell-derived brain organoids. In both dorsal and ventral forebrain STRADA knockout organoids, neurogenesis is delayed, with a predilection for progenitor renewal, increased proliferation and an expanded outer radial glia population. Ventrally, interneuron subtypes shift to an increase in neuropeptide Y-expressing cells. Inhibition of the mTOR pathway with rapamycin rescues most phenotypes. When mTOR pathway variants are present in all cells of the developing brain, overproduction of interneurons and altered interneuron cell fate may underlie mechanisms of megalencephaly, epilepsy, and cognitive impairment. Our findings suggest that mTOR inhibition during fetal brain development could be a potential therapeutic strategy in STRADA deficiency.

Indexed as

MegalencephalyNeurogenesisProsencephalonTOR Serine-Threonine KinasesCell DifferentiationCell ProliferationHumansInterneuronsOrganoidsSignal TransductionMTOR protein, humanTOR Serine-Threonine Kinasesbrain organoidcell fate specificationepilepsyinterneuron developmentmammalian target of rapamycinmechanistic target of rapamycinmTORmTORC1PMSE syndromeSTRADA

Identifiers

PMID41791387
PMCPMC13083799

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.