Evidence map›Paper›PMID 24565998›Full record

ArticleDevelopmental biology2014

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death.

Nathan J VanDusen, Joshua W Vincentz, Beth A Firulli, Marthe J Howard, Michael Rubart, Anthony B Firulli

Abstract read
In one paragraph

Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Rare TruncatingGenes · 2026
    Article
  2. Article
  3. Article
  4. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Hand Factors in Cardiac Development.Anatomical record (Hoboken, N.J. : 2007) · 2019
    Review
  11. Article
  12. Article
  13. Article
  14. Genetic tools for identifying and manipulating fibroblasts in the mouse.Differentiation; research in biological diversity · 2016
    Review
  15. Molecular networks underlying myofibroblast fate and fibrosis.Journal of molecular and cellular cardiology · 2016
    Review
  16. Article
  17. Article
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 at 2 institutions in 1 country.

Nathan J VanDusenRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5225, USA.
Joshua W VincentzRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5225, USA.
Beth A FirulliRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5225, USA.
Marthe J HowardDepartment of Neurosciences and Program in Neurosciences and Neurological Disorders, University of Toledo Health Sciences Campus, Toledo, OH 43614, USA.
Michael RubartRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5225, USA.
Anthony B FirulliRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202-5225, USA. Electronic address: tfirulli@iu.edu.
Indiana University School of MedicineUniversity of Toledo · US

Funding

MECHANISMS OF SYMPATHETIC NEURON DEVELOPMENTR01NS040644 · NINDS · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI HOWARD, MARTHE J · 2000 to 2010
$2.8M
Endocardial mechanisms of cardiac trabeculation and septationR01HL120920 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.8M
The role of Twist family bHLH factors in limb morphogenesisR01AR061392 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2011 to 2015
$1.7M
Cellular and Molecular Mechanisms of Left Ventricular Growth and MorphogenesisR01HL122123 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.6M
NHLBI NIH HHS R01 HL120920NHLBI NIH HHS R01 HL122123NIAMS NIH HHS R01 AR061392NIAMS NIH HHS R01 AR061392-03NINDS NIH HHS R01 NS040644NINDS NIH HHS R01NS040644
6 · The paper itself

Abstract

The Periostin Cre (Postn-Cre) lineage includes endocardial and neural crest derived mesenchymal cells of the cardiac cushions, neural crest-derived components of the sympathetic and enteric nervous systems, and cardiac fibroblasts. In this study, we use the Postn-Cre transgenic allele to conditionally ablate Hand2 (H2CKO). We find that Postn-Cre H2CKOs die shortly after birth despite a lack of obvious cardiac structural defects. To ascertain the cause of death, we performed a detailed comparison of the Postn-Cre lineage and Hand2 expression at mid and late stages of embryonic development. Gene expression analyses demonstrate that Postn-Cre ablates Hand2 from the adrenal medulla as well as the sphenopalatine ganglia of the head. In both cases, Hand2 loss-of-function dramatically reduces expression of Dopamine Beta Hydroxylase (Dbh), a gene encoding a crucial catecholaminergic biosynthetic enzyme. Expression of the genes Tyrosine Hydroxylase (Th) and Phenylethanolamine N-methyltransferase (Pnmt), which also encode essential catecholaminergic enzymes, were severely reduced in postnatal adrenal glands. Electrocardiograms demonstrate that 3-day postnatal Postn-Cre H2CKO pups exhibit sinus bradycardia. In conjunction with the aforementioned gene expression analyses, these results strongly suggest that the observed postnatal lethality occurs due to a catecholamine deficiency and subsequent heart failure.

Indexed as

AnimalsAnimals, NewbornBasic Helix-Loop-Helix ProteinsBradycardiaCell LineageIn Situ HybridizationMiceMice, KnockoutPolymerase Chain ReactionBasic Helix-Loop-Helix ProteinsHand2 protein, mouseBasic Helix-loop-Helix (bHLH) transcription factorBradycardiaHand2Heart developmentHeart failureSympathetic neurogenesis

Identifiers

PMID24565998
PMCPMC3990418
OpenAlexW2060258889

What OpenQuestion holds

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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.