Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates.
Dyneins have been implicated in left-right axis determination during embryonic development and in a variety of human genetic syndromes. In this paper, we study the recently discovered mouse dynein 2 light intermediate chain (mD2LIC), which is believed to be involved in retrograde intraflagella transport and which, like left-right dynein, is expressed in the node of the mouse embryo. Cells of the ventral node of mouse embryos lacking mD2LIC have an altered morphology and lack monocilia, and expression of Foxa2 and Shh in this structure is reduced or completely absent. At later stages, consistent with the absence of nodal cilia, mD2LIC is required for the establishment of the left-right axis and for normal expression of Nodal, and the ventral neural tube fails to express Shh, Foxa2 and Ebaf. mD2LIC also functions indirectly in the survival of anterior definitive endoderm and in the maintenance of the anterior neural ridge, probably through maintenance of Foxa2/Hnf3beta expression. Together, our results indicate that mD2LIC is required to maintain or establish ventral cell fates and for correct signalling by the organiser and midline, and they identify the first embryonic function of a vertebrate cytoplasmic dynein.
Rana
Amer Ahmed
AA
Division of Mammalian Development, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. a.rana@gurdon.cam.ac.uk
Barbera
Juan Pedro Martinez
JP
Rodriguez
Tristan A
TA
Lynch
Denise
D
Hirst
Elizabeth
E
Smith
James C
JC
Beddington
Rosa S P
RS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology*; D004398:Dyneins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018390:Gene Targeting; D008648:Mesoderm; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism; D020897:Organizers, Embryonic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D004398:Dyneins