Skeletal muscle deformity and neuronal disorder in Trio exchange factor-deficient mouse embryos.
Stephen J. O'Brien,Katja Seipel,Quintus G. Medley,Roderick T. Bronson,Rosalind A. Segal,Michel Streuli +5 more
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It is concluded thatTrio is essential for late embryonic development, and that Trio functions in fetal skeletal muscle formation and in the organization of neural tissues.Abstract:
Dbl-homology guanine nucleotide exchange factors (DH-GEFs) regulate actin cytoskeletal reorganization, cell adhesion, and gene transcription via activation of Rho GTPases. However, little is known about the physiological role of mammalian DH-GEFs during development. The DH-GEF family member Trio is of particular interest because it is a multifunctional protein possessing two GEF domains, as well as a protein serine/threonine kinase domain, and trio-like genes in Caenorhabditis elegans and Drosophila were shown to function in neural migration and axon guidance. To determine the role of Trio during mammalian development, we generated a mouse trio loss-of-function mutation (trio−/−). Trio function is essential during late embryonic development as genotype analysis indicated that trio−/− embryos died between embryonic day (E)-15.5 and birth, or shortly thereafter. In the trio−/− embryos, primary skeletal myofibers were relatively normal at E14.5, but by E18.5 highly unusual spherical myofibers accumulated. Trio deficiency may cause a defect in secondary myogenesis, as the appearance of the abnormal trio−/− skeletal myofibers temporally coincided with the onset of secondary myogenesis, and smaller secondary myofibers located adjacent to the primary myofibers were absent. The proliferation of trio−/− secondary myoblasts appeared normal, suggesting that Trio may regulate secondary myoblast alignment or fusion. trio−/− embryos also displayed aberrant organization in several regions within the brain, including the hippocampal formation and olfactory bulb. We thus conclude that Trio is essential for late embryonic development, and that Trio functions in fetal skeletal muscle formation and in the organization of neural tissues.read more
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GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
TL;DR: With 69 distinct homologues, Dbl-related GEFs represent the largest family of direct activators of Rho GTPases in humans, and they activate RhoGTPases within particular spatio-temporal contexts.
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Guanine nucleotide exchange factors for Rho GTPases: turning on the switch
Anja Schmidt,Alan Hall +1 more
TL;DR: All the evidence points to GEFs being the critical mediators of Rho GTPase activation, and this paper reviews the present understanding of how they do this.
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Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.
Kit Wong,Xiu Rong Ren,Yang Zhong Huang,Yi Xie,Guofa Liu,Harumi Saito,Hao Tang,Leng Wen,Susann M. Brady-Kalnay,Lin Mei,Jane Y. Wu,Wen Cheng Xiong,Yi Rao +12 more
TL;DR: It is reported here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs) that are expressed in regions responsive to Slit and demonstrated important roles for GAPs and Cdc42 in neuronal migration.
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The Evolution of Controlled Multitasked Gene Networks: The Role of Introns and Other Noncoding RNAs in the Development of Complex Organisms
John S. Mattick,M. J. Gagen +1 more
TL;DR: Network integration and multitasking using trans-acting RNA molecules produced in parallel with protein-coding sequences may underpin both the evolution of developmentally sophisticated multicellular organisms and the rapid expansion of phenotypic complexity into uncontested environments such as those initiated in the Cambrian radiation and those seen after major extinction events.
Journal ArticleDOI
Myoblast fusion: lessons from flies and mice
Susan M. Abmayr,Grace K. Pavlath +1 more
TL;DR: An overview of myoblast fusion in three model systems that have contributed much to understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells is provided.
References
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Paul Hasty,Paul Hasty,Allan Bradley,Julia Hsi Morris,Diane G. Edmondson,Judith M. Venuti,Eric N. Olson,William H. Klein +7 more
TL;DR: To test Myogenin's role in vivo, mice homozygous for a targeted mutation in the myogenin gene were generated and these mice survive fetal development but die immediately after birth and show a severe reduction of all skeletal muscle.
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Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.
TL;DR: Cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.
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Myogenin gene disruption results in perinatal lethality because of severe muscle defect
Yoko Nabeshima,Kazunori Hanaoka,Michiko Hayasaka,Eisaku Esuml,Shaowei Li,Ikuya Nonaka,Yo-ichi Nabeshima +6 more
TL;DR: Evidence that myogenin is crucial for muscle development in utero is shown and it is demonstrated that other members of the myogenic gene family cannot compensate for the defect.
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