Evidence map›Paper›PMID 35294885›Full record

ArticleCell reports2022

Tracheal separation is driven by NKX2-1-mediated repression of Efnb2 and regulation of endodermal cell sorting.

Ace E Lewis, Akela Kuwahara, Jacqueline Franzosi, Jeffrey O Bush

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
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

7 citing papers in PubMed, 13 citations in OpenAlex.

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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

4 authors at 2 institutions in 1 country.

Ace E LewisDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, Box 0512, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Akela KuwaharaDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, Box 0512, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Jacqueline FranzosiDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, Box 0512, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Jeffrey O BushDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Program in Craniofacial Biology, University of California, San Francisco, 513 Parnassus Avenue, Box 0512, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jeffrey.bush@ucsf.edu.
Broad Center · USUniversity of California, San Francisco · US

Funding

Mechanisms of Eph/Ephrin signaling in craniofacial morphogenesis and craniofrontonasal syndromeR01DE023337 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUSH, JEFFREY OHMANN · 2013 to 2021
$4.3M
Mechanisms of early tracheal specification and morphogenesisR01HL144785 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUSH, JEFFREY OHMANN · 2019 to 2022
$1.6M
NHLBI NIH HHS R01 HL144785NIDCR NIH HHS R01 DE023337
6 · The paper itself

Abstract

The mechanisms coupling fate specification of distinct tissues to their physical separation remain to be understood. The trachea and esophagus differentiate from a single tube of definitive endoderm, requiring the transcription factors SOX2 and NKX2-1, but how the dorsoventral site of tissue separation is defined to allocate tracheal and esophageal cell types is unknown. Here, we show that the EPH/EPHRIN signaling gene Efnb2 regulates tracheoesophageal separation by controlling the dorsoventral allocation of tracheal-fated cells. Ventral loss of NKX2-1 results in disruption of separation and expansion of Efnb2 expression in the trachea independent of SOX2. Through chromatin immunoprecipitation and reporter assays, we find that NKX2-1 likely represses Efnb2 directly. Lineage tracing shows that loss of NKX2-1 results in misallocation of ventral foregut cells into the esophagus, while mosaicism for Nkx2-1 generates ectopic NKX2-1/EPHRIN-B2 boundaries that organize ectopic tracheal separation. Together, these data demonstrate that NKX2-1 coordinates tracheal specification with tissue separation through the regulation of EPHRIN-B2 and tracheoesophageal cell sorting.

Indexed as

EndodermTracheaDigestive SystemEphrin-B2EsophagusEphrin-B2cell sortingendodermEph/ephrinephrin-B2esophagusforegutNkx2-1Sox2tracheatracheoesophageal fistula

Identifiers

PMID35294885
PMCPMC9033272
OpenAlexW4220929316

What OpenQuestion 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 OpenQuestion graph.