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The sinus venosus progenitors separate and
5 K" ^! s* ^1 l9 z0 Ediversify from the first and second heart fields6 K; }" X* Y7 o, p8 {7 g
early in development
+ Q3 ?. P8 }6 U$ f" v+ qMathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,
5 w% Z; g2 n. HCorrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,8 v+ y2 K" P5 L. B( I
Antoon F.M. Moorman1, and Vincent M. Christoffels 1*$ v4 ?4 c0 Y2 h
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,
1 e9 [8 y' r; _6 L& L1 U- YLondon, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,
/ a$ D" q1 i9 v1 p# t5 @Philadelphia, PA, USA
+ S5 w8 _- N; \+ CReceived 4 August 2009; revised 21 January 2010; accepted 26 January 2010# d4 U7 g+ Q# x/ `& ]
Time for primary review: 36 days
- G2 c+ V0 ^0 l- Z2 C, pAims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous
/ L; {& x- s: \8 P9 i( d+ E: @pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed
# f$ P% P- i" C( T4 I0 d$ E- z/ z$ Qto form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between
; D9 J( Z% s i, o: ?( C. ^these contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic0 [% |6 G: L1 n" U
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.
% A+ s2 Y$ | o' j9 Z) `7 [: uMethods; w- e8 Y" M V& [2 n% |
and results
2 @* b- S. P0 H5 WExplant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium.4 a6 ~/ }# [# G5 w/ F
Three-dimensional reconstruction of expression patterns showed that during heart tube elongation, the
2 A. S; |2 Q8 ^0 d; @) ~5 H4 A" j rTbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping; o1 p% f7 U5 M6 S7 T+ H
with the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,
9 q8 J- L& i. g% S) {. ugenetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not
9 ?1 R" \! f$ g1 M6 ?contribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling3 m1 O5 @+ s( q0 r/ V) @5 c
and expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of% f6 M! u3 W! v2 U; g# g4 i
splanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus5 y0 b4 N3 r3 F0 _ |$ p$ r
myocardium.5 ]8 f" F! ^# O$ ?$ S, ]
Conclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to& x9 n: J1 l& g- }
the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains1 v% F7 T+ g3 c+ A! f
spatially separated and genetically distinctive from the second heart field subpopulation.
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发表于 2010-5-6 21:16
