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The sinus venosus progenitors separate and
, X* N w d9 e3 d3 G' M3 L3 w& F. Ndiversify from the first and second heart fields0 \% w, \0 [0 w1 l
early in development
$ Y A1 k# s+ S. MMathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,
6 G5 d/ f1 ]% ICorrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,. X5 f2 G1 d* Q5 N) E
Antoon F.M. Moorman1, and Vincent M. Christoffels 1*
# J0 z) @. j0 x t1Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands; 2Division of Basic Medical Sciences, St George’s, University of London,+ }2 R8 [: i/ v/ f; V
London, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,9 n* q1 f$ w& S7 M ~7 Q W, u* O
Philadelphia, PA, USA8 p1 l) i9 h: D
Received 4 August 2009; revised 21 January 2010; accepted 26 January 20104 h& [0 X3 J+ e- ^% R
Time for primary review: 36 days9 U" x* y$ u; ]8 F
Aims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous; ^1 j# H+ b( M2 F% r3 Y! K& X
pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed% [4 u8 ^6 d( b( F+ e
to form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between
+ F/ Z# B( j. ?1 \these contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic& _* Z: o9 ]' R$ z: h
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.$ C# D& v; p, O1 G3 _5 N: B. `/ q
Methods, I3 W- g: d! s) E9 B
and results4 T& V& D! s3 v5 f
Explant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium., T; i( o; z- W7 O* ^
Three-dimensional reconstruction of expression patterns showed that during heart tube elongation, the+ _6 @* {0 v" M: B& A- ^
Tbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping7 B4 w( e# K1 t' g# W) i3 C- w9 D- F
with the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,; {5 u, k6 O5 q. e1 d% {5 I
genetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not* i" i. x% d, u& L* m9 `+ m
contribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling
( I3 ~7 }( Z2 |- {" Y" |. Iand expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of
7 I- h) _$ N" i7 M6 U) esplanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus4 t: Q( ^3 _! D; v$ p" o3 B
myocardium.
6 x1 u e( \3 r a8 n9 KConclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to
6 {6 v& S& R4 b' d7 z/ _the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains8 J/ I [5 C0 F7 L7 \1 d
spatially separated and genetically distinctive from the second heart field subpopulation., T7 A# n7 k' g: M: m* T7 [- i# I
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发表于 2010-5-6 21:16
