Research Report 2010 - MDC

Control Olig3 -/-ABFigure 2. Genetic lineage tracing in heterozygous and homozygous Olig3 mutant mice. Cre expression that is driven by the Olig3 locus inducesrecombination in the Rosa26R allele, allowing expression of a lacZ gene. The active, recombined lacZ gene is inherited in cells that expressed haveexpressed Olig3 (and therefore the cre recombinase) at earlier stages in development. Cells that express lacZ were identified by X-Gal staining(blue). Shown is the medulla oblongata of control (A: Olig3CreERT2/+; Rosa26R) and Olig3 mutant (B: Olig3CreERT2/-; Rosa26R) mice at E18.5.Arrowheads indicate cuneate nucleus (Cu), inferior olivary nucleus (ION), nucleus of the solitary tract (NTS) and lateral reticular nucleus (LRt).Note the absence of inferior olivary nucleus and nucleus of the solitary tract, as well as the changed distribution of neurons in the dorsal hindbrainof the homozygous Olig3 mutant mice.alar plate of the hindbrain. We found that the Olig3+progenitor domain gives rise to several neuronal subtypesin the dorsal alar plate. We used genetic lineagetracing to demonstrate that these neurons settle in thenucleus of the solitary tract and to precerebellar nuclei.The fate of class these neurons is not correctly determinedin Olig3 mutant mice, and as a consequence, thenucleus of the solitary tract does not form, and precerebellarnuclei, such as the inferior olivary nucleus, areabsent or small.The small G-proteins Rac1 and Cdc42 are essentialfor myoblast fusion in the mouseElena Vasyutina, Benedetta Martarelli, Hagen Wende(in collaboration with Cord Brakebusch, University ofCopenhagen)Skeletal muscle fibers are syncytia that arise by thefusion of myogenic cells. Mononucleated myogeniccells, the myoblasts, fuse with each other to form multinucleatedmyotubes. During development and in theadult, myoblast fusion allows generation, growth andrepair of muscle fibers. Rac1 and Cdc42 are small G-proteinsthat regulate actin dynamics. In Drosophila, RacGTPases, dRac1 and dRac2, act downstream of cell adhesionmolecules to control cytoskeletal rearrangements,and myoblast fusion.We analyzed the function of Rac1 and Cdc42 in myogenesisusing conditional mutagenesis in mice. Weshowed that in the absence of Rac1 and Cdc42,myoblast fusion is severely compromised in vivo and invitro. The deficit in fusion of Rac1 or Cdc42 mutantmyoblasts correlated with a deficit in the recruitmentof actin fibers and vinculin to myoblast contact sites.Moreover, we demonstrated that Rac1 and Cdc42 arerequired in both fusion partners. Thus, our analysisdemonstrated that the function of Rac1 is evolutionarilyconserved from insects to mammals, and that Cdc42,a molecule hitherto not implicated in myoblast fusion,is essential for the fusion of murine myoblasts.152 Function and Dysfunction of the Nervous System