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The sinus venosus progenitors separate and# V" H' f. \. Y$ p$ \2 P! |
diversify from the first and second heart fields
0 A9 V! M) q! C/ b/ n. Cearly in development
% t5 H1 f" o* A, T# K2 w, yMathilda T.M. Mommersteeg1, Jorge N. Domı´nguez2, CorneliaWiese1, Julia Norden3,, Y, S% J* \& Z! {* w. M
Corrie de Gier-de Vries1, John B.E. Burch4, Andreas Kispert3, Nigel A. Brown2,: }9 N2 o+ s- {, D* x, P
Antoon F.M. Moorman1, and Vincent M. Christoffels 1*- J4 C- F4 V8 w
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,# F8 M0 s# m. ?* j9 I$ v7 ~
London, UK; 3Institut fu¨r Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany; and 4Cell and Developmental Biology Program, Fox Chase Cancer Center,
! _. f6 M' t" S! hPhiladelphia, PA, USA K1 N w5 c& v, @8 z0 S% @
Received 4 August 2009; revised 21 January 2010; accepted 26 January 2010% j* t9 j9 g4 r0 Q6 k
Time for primary review: 36 days
# D/ e; C* R' {( @; @' h' \Aims During development, the heart tube grows by differentiation of Isl1þ/Nkx2-5þ progenitors to the arterial and venous, c/ i% w4 y( j: h8 Y) D# I
pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18þ progenitors were proposed
! q$ v+ {, S/ Y9 r; n6 P- Oto form the Tbx18þ/Nkx2-52 sinus venosus and proepicardium. To elucidate the relationship between
1 {$ x9 q# O4 t+ H* xthese contributions, we investigated the origin of the Tbx18þ sinus venosus progenitor population in the cardiogenic1 ?7 X; T1 W) E3 g
mesoderm and its spatial and temporal relation to the second heart field during murine heart development.% ]; o5 I# y6 {
Methods8 K ^3 t: x; J/ Y) Z
and results
( l0 T- l3 X2 J+ O* N/ u% DExplant culture revealed that the Tbx18þ cell population has the potential to form Nkx2-52 sinus venosus myocardium.$ c& F \- \6 F/ Y$ M$ @
Three-dimensional reconstruction of expression patterns showed that during heart tube elongation, the( w) w4 y8 S4 ]7 }
Tbx18þ progenitors remained spatially and temporally separate from the Isl1þ second heart field, only overlapping
# l6 L7 [" R7 o2 U F. n! t' F6 u' Awith the Isl1þ domain at the right lateral side of the inflow tract, where the sinus node developed. Consistently,% g2 v m6 q% n/ V' m0 \
genetic lineage analysis revealed that the Tbx18þ descendants formed the sinus venosus myocardium, but did not! _1 ?0 n5 T" a) G" `
contribute to the pulmonary vein myocardium that developed in the Isl1þ second heart field. By means of DiI labelling
: B: k! y* g4 H# [' Cand expression analysis, the origin of the sinus venosus progenitor population was traced to the lateral rim of; `. z' D1 e% Y5 ~
splanchnic mesoderm that down-regulated Nkx2-5 expression 2 days before its differentiation into sinus venosus
; O8 ]- g; h. X* T) [) x+ jmyocardium.% W) u5 M0 k' ~
Conclusion Our data indicate that the cardiogenic mesoderm contains an additional progenitor subpopulation that contributes to W. f8 `8 P7 A
the sinus venosus myocardium. After patterning of the cardiogenic mesoderm, this progenitor population remains: v" e7 X) G" G( h% R
spatially separated and genetically distinctive from the second heart field subpopulation.
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发表于 2010-5-6 21:16
