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The sinus venosus progenitors separate and
/ E7 n+ q9 H6 \diversify from the first and second heart fields# x- H: @: j Q; @5 L( t
early in development; }; M* ]5 Y. ]8 g8 A7 v4 F& P
Mathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,- |, _: v; {' D1 b, @# |; f; E
Corrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,
2 o7 V- W A; v4 q# ` F9 OAntoon F.M. Moorman1, and Vincent M. Christoffels 1*) j V5 _8 }, A
1Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands; 2Division of Basic Medical Sciences, St George’s, University of London,, G* Y. ~/ s( e8 I$ F
London, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,
6 v$ J3 x8 y+ UPhiladelphia, PA, USA8 u1 T ^' \4 c6 R
Received 4 August 2009; revised 21 January 2010; accepted 26 January 20103 o9 x. h7 o3 w: f/ m. x6 s' t
Time for primary review: 36 days5 L( t) G+ S% Z# y) S, B9 z. Y
Aims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous/ K; G0 ?3 v3 X! \
pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed
& b( z/ U. R4 {to form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between
+ l( _" G) B, n& cthese contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic( c5 Y/ l* S" k" |) O8 [
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.# c3 t6 W' T" G8 I
Methods
4 B3 x/ Y# X& u' L8 e5 wand results
9 |3 O' [5 [0 cExplant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium.
# c% ~3 f) c, o! sThree-dimensional reconstruction of expression patterns showed that during heart tube elongation, the5 l9 o7 w; X0 b) g$ Z' ~& C
Tbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping$ |% X6 @5 Z! Q
with the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,
+ u Q) C& f9 |9 d) w7 A7 a; [genetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not
2 {1 ^" `7 }8 b" L; v& @' J scontribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling
9 l+ ?9 x- L6 |* H( X. M& _and expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of
+ n$ U5 B- j0 \2 V1 J ~2 Hsplanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus
' m4 c! W* I _+ }$ R; _myocardium.
- Q! z) ~$ f/ r! f1 F" IConclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to0 a: W& A4 `2 P1 Q" J' ?
the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains
; p) L1 }* J0 J7 W+ `' |1 Ospatially separated and genetically distinctive from the second heart field subpopulation.3 {" J2 K) Y1 @5 r# Q r5 a/ Z
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发表于 2010-5-6 21:16
