title: Evolution and development of ventricular septation in the amniote heart.
abstract: During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lambertus J
authors.initials: LJ
authors.lastname: Wisse
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Margot M
authors.initials: MM
authors.lastname: Bartelings
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sonja
authors.initials: S
authors.lastname: Everts
authors.affiliation: Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: Tamara
authors.initials: T
authors.lastname: Hoppenbrouwers
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Boudewijn P T
authors.initials: BP
authors.lastname: Kruithof
authors.affiliation: Department of Anatomy, Embryology and Physiology, AMC Amsterdam, Amsterdam, The Netherlands; Department of Bioscience-Zoophysiology, Aarhus University, Aarhus, Denmark.
authors.forename: Bjarke
authors.initials: B
authors.lastname: Jensen
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul W
authors.initials: PW
authors.lastname: de Bruin
authors.affiliation: Laboratory for Evolutionary Morphology, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hirasawa
authors.affiliation: Laboratory for Evolutionary Morphology, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kuratani
authors.affiliation: Naturalis Biodiversity Center, Darwinweg 2, Leiden, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Vonk
authors.affiliation: Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: Jeanne M M S
authors.initials: JM
authors.lastname: van de Put
authors.affiliation: Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: Merijn A
authors.initials: MA
authors.lastname: de Bakker
authors.affiliation: Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Richardson
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004606:Elephants; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology*; D006346:Heart Septum / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D038081:Organogenesis / Q000502:physiology*; D010496:Pericardium / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012104:Reptiles; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5