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-von der Lohe, Anthony Firulli

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (H2. CKO). We find that Postn-Cre H2. CKOs 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 H2. CKO 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.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalDevelopmental Biology
Volume388
Issue number2
DOIs
StatePublished - Apr 15 2014

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Bradycardia
Neural Crest
Gene Expression
Phenylethanolamine N-Methyltransferase
Population
Enteric Nervous System
Dopamine beta-Hydroxylase
Adrenal Medulla
Sympathetic Nervous System
Tyrosine 3-Monooxygenase
Enzymes
Adrenal Glands
Ganglia
Catecholamines
Embryonic Development
Cause of Death
Electrocardiography
Heart Failure
Fibroblasts
Alleles

Keywords

  • Basic Helix-loop-Helix (bHLH) transcription factor
  • Bradycardia
  • Hand2
  • Heart development
  • Heart failure
  • Sympathetic neurogenesis

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death. / VanDusen, Nathan J.; Vincentz, Joshua W.; Firulli, Beth A.; Howard, Marthe J.; Rubart-von der Lohe, Michael; Firulli, Anthony.

In: Developmental Biology, Vol. 388, No. 2, 15.04.2014, p. 149-158.

Research output: Contribution to journalArticle

VanDusen, Nathan J. ; Vincentz, Joshua W. ; Firulli, Beth A. ; Howard, Marthe J. ; Rubart-von der Lohe, Michael ; Firulli, Anthony. / Loss of Hand2 in a population of Periostin lineage cells results in pronounced bradycardia and neonatal death. In: Developmental Biology. 2014 ; Vol. 388, No. 2. pp. 149-158.
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