Hand2 loss-of-function in hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development

Ralston M. Barnes, Beth A. Firulli, Nathan J. Vandusen, Yuka Morikawa, Simon Conway, Peter Cserjesi, Joshua W. Vincentz, Anthony Firulli

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Rationale: The basic helix-loop-helix (bHLH) transcription factors Hand1 and Hand2 are essential for embryonic development. Given their requirement for cardiogenesis, it is imperative to determine their impact on cardiovascular function. Objective: To deduce the role of Hand2 within the epicardium. Zmethod and Results: We engineered a Hand1 allele expressing Cre recombinase. Cardiac Hand1 expression is largely limited to cells of the primary heart field, overlapping little with Hand2 expression. Hand1 is expressed within the septum transversum, and the Hand1 lineage marks the proepicardial organ and epicardium. To examine Hand factor functional overlap, we conditionally deleted Hand2 from Hand1-expressing cells. Hand2 mutants display defective epicardialization and fail to form coronary arteries, coincident with altered extracellular matrix deposition and Pdgfr expression. Conclusions: These data demonstrate a hierarchal relationship whereby transient Hand1 septum transversum expression defines epicardial precursors that are subsequently dependent on Hand2 function.

Original languageEnglish
Pages (from-to)940-949
Number of pages10
JournalCirculation Research
Volume108
Issue number8
DOIs
StatePublished - Apr 15 2011

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Pericardium
Coronary Vessels
Basic Helix-Loop-Helix Transcription Factors
Embryonic Development
Extracellular Matrix
Hand
Alleles
Cre recombinase

Keywords

  • bHLH
  • epicardium
  • Hand1
  • Hand2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hand2 loss-of-function in hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development. / Barnes, Ralston M.; Firulli, Beth A.; Vandusen, Nathan J.; Morikawa, Yuka; Conway, Simon; Cserjesi, Peter; Vincentz, Joshua W.; Firulli, Anthony.

In: Circulation Research, Vol. 108, No. 8, 15.04.2011, p. 940-949.

Research output: Contribution to journalArticle

Barnes, Ralston M. ; Firulli, Beth A. ; Vandusen, Nathan J. ; Morikawa, Yuka ; Conway, Simon ; Cserjesi, Peter ; Vincentz, Joshua W. ; Firulli, Anthony. / Hand2 loss-of-function in hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development. In: Circulation Research. 2011 ; Vol. 108, No. 8. pp. 940-949.
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