Evidence map›Paper›PMID 29507412›Full record

ArticleNature neuroscience2018

Developmentally primed cortical neurons maintain fidelity of differentiation and establish appropriate functional connectivity after transplantation.

Thomas V Wuttke, Foivos Markopoulos, Hari Padmanabhan, Aaron P Wheeler, Venkatesh N Murthy, Jeffrey D Macklis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Capturing the Electrical Activity of all Cortical Neurons: Are Solutions Within Reach?Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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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

6 authors.

Thomas V Wuttke *Dept. of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Foivos Markopoulos *Dept. of Molecular and Cellular Biology, and Center for Brain Science, Harvard University, Cambridge, MA, USA.
Hari PadmanabhanDept. of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Aaron P WheelerDept. of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Venkatesh N MurthyDept. of Molecular and Cellular Biology, and Center for Brain Science, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2443-4252
Jeffrey D MacklisDept. of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. jeffrey_macklis@harvard.edu.ORCID http://orcid.org/0000-0003-3662-9698

Funding

Molecular Controls over Neurogenesis, Subtype Development, and Diversity of Cortical Output Projection NeuronsR01NS045523 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MACKLIS, JEFFREY D · 2002 to 2020
$5.4M
Neocortical Precursor Transplant for Circuitry RepairR37NS041590 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MACKLIS, JEFFREY D · 2004 to 2010
$2.9M
Molecular Mechanisms of CTIP2 Function in Corticospinal Motor Neuron DevelopmentR01NS075672 · NINDS · HARVARD UNIVERSITY · PI MACKLIS, JEFFREY D · 2012 to 2016
$1.8M
Optogenetic studies of mouse olfactionR01DC011291 · NIDCD · HARVARD UNIVERSITY · PI MURTHY, VENKATESH N · 2011 to 2015
$1.7M
Cortico-Spinal Repopulation from Precursors for RepairR01NS049553 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MACKLIS, JEFFREY D · 2004 to 2007
$1.6M
NEOCORTICAL PRECURSOR TRANSPLANTS FOR CIRCUITRY REPAIRR01NS041590 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MACKLIS, JEFFREY D · 2000 to 2003
$1.5M
Molecular development and diversity of callosal projection neuronsR56NS093376 · NINDS · HARVARD UNIVERSITY · PI MACKLIS, JEFFREY D · 2016 to 2016
$424k
NIDCD NIH HHS R01 DC011291NINDS NIH HHS R01 NS041590NINDS NIH HHS R01 NS045523NINDS NIH HHS R01 NS049553NINDS NIH HHS R01 NS075672NINDS NIH HHS R37 NS041590NINDS NIH HHS R56 NS093376
6 · The paper itself

Abstract

Repair of complex CNS circuitry requires newly incorporated neurons to become appropriately, functionally integrated. One approach is to direct differentiation of endogenous progenitors in situ, or ex vivo followed by transplantation. Prior studies find that newly incorporated neurons can establish long-distance axon projections, form synapses and functionally integrate in evolutionarily old hypothalamic energy-balance circuitry. We now demonstrate that postnatal neocortical connectivity can be reconstituted with point-to-point precision, including cellular integration of specific, molecularly identified projection neuron subtypes into correct positions, combined with development of appropriate long-distance projections and synapses. Using optogenetics-based electrophysiology, experiments demonstrate functional afferent and efferent integration of transplanted neurons into transcallosal projection neuron circuitry. Results further indicate that 'primed' early postmitotic neurons, including already fate-restricted deep-layer projection neurons and/or plastic postmitotic neuroblasts with partially fate-restricted potential, account for the predominant population of neurons capable of achieving this optimal level of integration.

Indexed as

Neocortex6-Cyano-7-nitroquinoxaline-2,3-dioneAction PotentialsAnimalsAnimals, NewbornCell Adhesion Molecules, NeuronalCell DifferentiationDNA-Binding ProteinsEmbryo, MammalianExcitatory Amino Acid AntagonistsGene Expression Regulation, DevelopmentalMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsNeurons2-amino-5-phosphopentanoic acid6-Cyano-7-nitroquinoxaline-2,3-dioneBcl11b protein, mouseCell Adhesion Molecules, NeuronalDNA-Binding ProteinsExcitatory Amino Acid AntagonistsNerve Tissue ProteinsRepressor ProteinsStab2 protein, mouseSynaptophysinTranscription FactorsTumor Suppressor ProteinsValineZfp312 protein, mouseZfpm2 protein, mouse

Identifiers

PMID29507412
PMCPMC5876138

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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.