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. METHOD 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.
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. METHOD 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.
Authors: Mingfu Wu; Christopher L Smith; James A Hall; Ivy Lee; Kate Luby-Phelps; Michelle D Tallquist Journal: Dev Cell Date: 2010-07-20 Impact factor: 12.270
Authors: Kristen L Holler; Tyler J Hendershot; Sophia E Troy; Joshua W Vincentz; Anthony B Firulli; Marthe J Howard Journal: Dev Biol Date: 2010-02-06 Impact factor: 3.582
Authors: David Y Rhee; Xiao-Qing Zhao; Richard J B Francis; Guo Ying Huang; John D Mably; Cecilia W Lo Journal: Development Date: 2009-09 Impact factor: 6.868
Authors: Beth A Firulli; Robyn K Fuchs; Joshua W Vincentz; David E Clouthier; Anthony B Firulli Journal: Development Date: 2014-08 Impact factor: 6.868
Authors: Nathan J VanDusen; Joshua W Vincentz; Beth A Firulli; Marthe J Howard; Michael Rubart; Anthony B Firulli Journal: Dev Biol Date: 2014-02-22 Impact factor: 3.582
Authors: Ramji K Bhandari; Ellyn N Schinke; Md M Haque; Ingrid Sadler-Riggleman; Michael K Skinner Journal: Biol Reprod Date: 2012-12-06 Impact factor: 4.285
Authors: Nathan J VanDusen; Jose Casanovas; Joshua W Vincentz; Beth A Firulli; Marco Osterwalder; Javier Lopez-Rios; Rolf Zeller; Bin Zhou; Joaquim Grego-Bessa; José Luis De La Pompa; Weinian Shou; Anthony B Firulli Journal: Cell Rep Date: 2014-12-11 Impact factor: 9.423