title: Hand2 loss-of-function in Hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Riley Heart Research Center, Wells Center for Pediatric Research, Division of Pediatric Cardiology, Departments of Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, 46202-5225, USA.
authors.forename: Ralston M
authors.initials: RM
authors.lastname: Barnes
authors.forename: Beth A
authors.initials: BA
authors.lastname: Firulli
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: VanDusen
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Peter
authors.initials: P
authors.lastname: Cserjesi
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Vincentz
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Firulli
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010496:Pericardium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C095572:Hand1 protein, mouse; C498766:Hand2 protein, mouse