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The sinus venosus progenitors separate and5 o$ u3 {0 M" L. |( Q
diversify from the first and second heart fields$ j( }! s: I( M( ]+ y; f' B& |/ S
early in development
0 q& q6 L7 }$ v' ~0 J( y5 N# kMathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,
) ? h; t( v% A$ rCorrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,
2 h+ j V8 }. R+ iAntoon F.M. Moorman1, and Vincent M. Christoffels 1*
2 I8 S0 |4 N/ N% h8 z; f1Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands; 2Division of Basic Medical Sciences, St George’s, University of London,9 I3 k% e, i+ ]2 n9 R8 R3 G
London, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,0 L+ O/ u0 w4 E! r! N3 F# I/ u2 H0 l
Philadelphia, PA, USA" O: O0 ]) \- _1 P( U, q/ {2 V6 S
Received 4 August 2009; revised 21 January 2010; accepted 26 January 2010 z+ h* G& O# w: V# U R$ O) r
Time for primary review: 36 days) N$ T7 w( o: h7 e' p' S& A# I
Aims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous
" s+ x; s. \( V' g; Epole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed
0 _' X+ w$ o) T+ lto form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between
$ V2 q% x& Q e+ Othese contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic% R$ }' S j- r
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.! N+ o- N+ Y; e( f, n# e& `. h0 Z+ ~
Methods3 M& E: H2 D1 X3 X# S
and results
* b3 U! \# ?3 ]: ]Explant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium.
- y7 v. c* S9 w% v8 O. lThree-dimensional reconstruction of expression patterns showed that during heart tube elongation, the1 J7 [) U. c4 J) l
Tbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping+ d# Z: Y2 u& v# d2 Z* x7 r
with the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,+ H a; \# O5 P. S# N
genetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not9 A6 f& N+ N' h. |
contribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling2 E8 g9 g! p b$ o5 A) J
and expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of
3 R: t$ X" C* ^- \' {. G9 W% {0 B usplanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus, K% g; l- M5 \% w4 [1 y
myocardium.
2 c9 ~9 A* T& U/ x7 e; |6 U) cConclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to
9 l' ^0 a4 U! Q. r% J4 Ithe sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains% H M( x/ N6 N- [
spatially separated and genetically distinctive from the second heart field subpopulation.
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发表于 2010-5-6 21:16
