The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain

Fate-mapping experiments in the mouse have revealed that the primitive stre ak can be divided into three functional regions': the proximal region gives rise to germ cells and the extra-embryonic mesoderm of the yolk sac; the d istal region generates cardiac mesoderm and node-derived axial mesendoderm; and the middle streak region produces the paraxial, intermediate and later al plate mesoderm of the trunk. To gain insight into the mechanisms that me diate the assembly of the primitive streak into these functional regions, w e have cloned and functionally identified the gene disrupted in the amnionl ess (amn) mouse, which has a recessive, embryonic lethal mutation that inte rferes specifically with the formation and/or specification of the middle p rimitive streak region during gastrulation(2). Here we report that the gene Amn encodes a novel type I transmembrane protein that is expressed exclusi vely in the extra-embryonic visceral endoderm layer during gastrulation. Th e extracellular region of the Amn protein contains a cysteine-rich domain w ith similarity to bone morphogenetic protein (BMP)-binding cysteine-rich do mains in chordin, its Drosophila melanogaster homolog (Short: gastrulation) and procollagen IIA (ref. 3). Our findings indicate that Amn may direct th e production of trunk mesoderm derived from the middle streak by acting in the underlying visceral endoderm to modulate a BMP signaling pathway.