Fig. 7. Model for independent functions of Bmp4 in node and primitive streak morphogenesis, and LR asymmetry. (A) Pre- to early-streak stage; lateral view. Bmp4 produced in the ExE patterns the proximodistal axis of the epiblast and thereby plays a role in specifying cell fates along the anteroposterior axis of the future primitive streak. The most proximal cells (black circle) will give rise (yellow arrows) to the precursors of allantois, PGCs and ExM, which will translocate posteriorly (blue/green striped arrow), while the more distal precursors of embryonic mesoderm move anteriorly and laterally (red arrows). Fgf8 is expressed in the posteroproximal epiblast. (B) The presomite stage; ventral view. Progenitors of the node are thought to lie in the mid-anterior primitive streak and move anteriorly to be incorporated into the node (red arrows). This morphogenetic process is dependent on Bmp4 expression in the ExE (see A) and Fgf8 in the primitive streak (Sun et al., 1999). We speculate that Bmp4 produced in the ExM and/or posterior mesoderm (PM) positively regulates an unknown gene X that initiates the expression of Nodal (broken black arrows) in the periphery of the node (purple). Nodal flow (left-pointing black arrows) generates enrichment of left-side Nodal expression in the periphery of the node. The future Nodal expression in the left LPM is possibly initiated by Nodal protein diffusing from the node (broken blue arrow). (C) The two- to eight-somite stage. Bmp4 in the LPM is required for Nodal expression in the LPM (broken blue arrow). Nodal produced in the node may maintain the expression of cryptic that permits the expression of left-side determinant genes such as Nodal in the left LPM (broken black arrows).

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