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The sinus venosus progenitors separate and
& p' Z3 t, `9 x- Ddiversify from the first and second heart fields
& `% v0 c; G! Z7 V: Iearly in development4 [7 y8 L' z# |, P# f
Mathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,) ?& h( y# D l
Corrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,
9 G4 e+ T H1 n$ k: w) uAntoon F.M. Moorman1, and Vincent M. Christoffels 1*
$ h, X) x) |! u7 v3 T. n1Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands; 2Division of Basic Medical Sciences, St George’s, University of London,
5 |/ M! h1 J: a/ `: H# W4 MLondon, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,
( T* s% {% j) s) |! x0 A) mPhiladelphia, PA, USA/ p& y" I {: v; R
Received 4 August 2009; revised 21 January 2010; accepted 26 January 2010$ U# c- G$ V4 t) g \
Time for primary review: 36 days
7 H0 i; B+ Q4 W% U9 \ OAims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous
- o4 Z+ E9 k* }4 E, V7 ~5 ~pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed
1 Z4 P3 v- i5 tto form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between* D7 X& [3 @7 m
these contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic: p2 {4 a" r1 x# v E% w& ^7 U
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.
9 f% ^% T, J& i) s y" R XMethods7 {+ {. Z, I) k5 f/ V
and results: J# S7 C: f f8 A2 p# r/ z2 D1 X
Explant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium.; L( ]! W1 U5 d. Y# O4 _% g: I! e
Three-dimensional reconstruction of expression patterns showed that during heart tube elongation, the$ B9 l) T/ W6 n7 E K3 E
Tbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping: w3 Y! S, v# W7 g" c9 f$ y% M8 B. j
with the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,
2 w0 K9 `( L( [* N% ~genetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not
! C* j4 U0 H: M( c8 Pcontribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling+ ^& S, Q- J- G6 x
and expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of
8 h8 ?+ p7 ]- V1 ]8 Q4 asplanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus
! ^5 D0 n" w! \5 J# x+ gmyocardium.
6 ^* _/ j$ ^1 Q' n( k; s+ jConclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to1 p1 X* N" _) o+ H( Z- y
the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains
! _7 d* Y# p0 t# Lspatially separated and genetically distinctive from the second heart field subpopulation.
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发表于 2010-5-6 21:16
