Nodal signalling in the epiblast patterns the early mouse embryo.
Shortly after implantation the mouse embryo comprises three tissue layers. The founder tissue of the embryo proper, the epiblast, forms a radially symmetric cup of epithelial cells that grows in close apposition to the extra-embryonic ectoderm and the visceral endoderm. This simple cylindrical structure exhibits a distinct molecular pattern along its proximal-distal axis. The anterior-posterior axis of the embryo is positioned later by coordinated cell movements that rotate the pre-existing proximal-distal axis. The transforming growth factor-beta family member Nodal is known to be required for formation of the anterior-posterior axis. Here we show that signals from the epiblast are responsible for the initiation of proximal-distal polarity. Nodal acts to promote posterior cell fates in the epiblast and to maintain molecular pattern in the adjacent extra-embryonic ectoderm. Both of these functions are independent of Smad2. Moreover, Nodal signals from the epiblast also pattern the visceral endoderm by activating the Smad2-dependent pathway required for specification of anterior identity in overlying epiblast cells. Our experiments show that proximal-distal and subsequent anterior-posterior polarity of the pregastrulation embryo result from reciprocal cell-cell interactions between the epiblast and the two extra-embryonic tissues.
Brennan
J
J
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Lu
C C
CC
Norris
D P
DP
Rodriguez
T A
TA
Beddington
R S
RS
Robertson
E J
EJ
D000818:Animals; D019521:Body Patterning; D016764:Cell Polarity; D004268:DNA-Binding Proteins / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D055457:Nodal Protein; D015398:Signal Transduction; D051899:Smad2 Protein; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta