Gamma Tropomyosin Gene Products Are Required for Embryonic Development

Abstract

The actin filament system is essential for many cellular functions, including shape, motility, cytokinesis, intracellular trafficking, and tissue organization. Tropomyosins (Tms) are rod-like components of most actin filaments that differentially affect their stability and flexibility. The Tm gene family consists of four genes, ␣Tm, ␤Tm, ␥Tm (Tm5 NM, where "NM" indicates "nonmuscle"), and ␦Tm (Tm4). Multiple isoforms of the Tm family are generated by alternative splicing of three of these genes, and their expression is highly regulated. Extensive spatial and temporal sorting of Tm isoforms into different cellular compartments has been shown to occur in several cell types. We have addressed the function of the low-molecular-weight Tms encoded by the ␥Tm gene by eliminating the corresponding amino-terminal coding sequences from this gene. Heterozygous mice were generated, and subsequent intercrossing of the F 1 pups did not result in any viable homozygous knockouts. Genotype analysis of day 2.5 morulae also failed to detect any homozygous knockouts. We have failed in our attempts to delete the second allele and generate in vitro double-knockout cells, although 51 clones displayed homologous recombination back into the originally targeted locus. We therefore conclude that lowmolecular-weight products from the ␥Tm gene are essential for both embryonic development and cell survival.

Non-muscle tropomyosin (Tpm3) is crucial for asymmetric cell division and maintenance of cortical integrity in mouse oocytes

“…We focused on Tpm3, which is also known as gamma-tropomyosin, because this is the primary tropomyosin found at the cortex of non-muscle cells 9 and its knockout causes embryonic lethality in mouse. 17,18 Tpm3 mRNA was detected at all stages of oocyte maturation, indicating that Tpm3 is expressed during maturation of mouse oocytes (Fig. 1A).…”

“…14,15 Tropomyosins are essential for cytokinesis in fission yeast, 16 and knockout of the non-muscle gamma-tropomyosin (also known as Tpm3) gene causes embryonic lethality in mouse. 17,18 However, the exact roles of tropomyosins in oocyte maturation and embryogenesis are poorly understood.…”

Tropomyosin – master regulator of actin filament function in the cytoskeleton

“…All four mammalian Tpm genes (Tpm1, Tpm2 Tpm3, Tpm4) are expressed in mouse embryonic stem cells (Muthuchamy et al, 1993;Hook et al, 2004). Despite this, it has so far been impossible to delete both copies of the Tpm3 gene (Hook et al, 2004) because all Tpm3-knockout mice embryos died prior to implantation in the uterus.…”

Cell biology of embryonic migration

“…Mouse knockouts of cell migration components or other proteins with direct effects on cell migration Protein Function Type Phenotype Reference α skeletal muscle actin Actin Cytoskeleton Total Postnatal death at P1-9, marked loss of body weight; upregulation of other actin isoforms (Crawford et al, 2002) α smooth muscle actin Actin Cytoskeleton Total Viable; impaired vascular contractility and blood pressure homeostasis; upregulation of other actin isoforms (Schildmeyer et al, 2000) α cardiac actin Actin Cytoskeleton Total Perinathal lethality; cardiac hypertrophy and heart muscle abnormalities; upregulation of other actin isoforms (Kumar et al, 1997) β non-muscle actin Actin Cytoskeleton Total Death after E9.5 (Shawlot et al, 1998) γ non-muscle actin Actin Cytoskeleton Skeletal muscle-specific Muscle weakness, necrosis and degeneration (Sonnemann et al, 2006) Tropomyosin Actin Cytoskeleton Total Death before morula stage (Hook et al, 2004) Mena Actin Cytoskeleton Total Viable, with misrouted axons and defects in the nervous system (Lanier et al, 1999) Mena, VASP, Evl triple null Actin Cytoskeleton Total Defects in brain development, neuritogenesis, and neural tube closure Filamin-B Actin Cytoskeleton Total Skeletal malformations and impaired microvascular development (Zhou et al, 2007) Gelsolin (or ADF) Actin Cytoskeleton Total Defects in fibroblast and platelet motility and lamellar responses (Witke et al, 1995) Nonmuscle myosin II-B Actin Cytoskeleton Total Embryonic and perinatal lethality with severe heart defects (Tullio et al, 1997) Myosin heavy chain II-A Actin Cytoskeleton Total Failure in embryonic patterning, embryonic lethality by E7.5 (Conti et al, 2004) Cardiac alpha myosin, heavy chain Actin Cytoskeleton Total Embryonic lethality between E11 and 12 with gross heart defects (Jones, 1996) (Imamoto and Soriano, 1993;Nada et al, 1993) Ephrin B1 Transmembrane signaling Total Neural crest cell misguidance (cranial and cardiac, but not trunk) (Davy et al, 2004) Angiomotin Transmembrane signaling Total Death between E11-E11.5, severe vascular insufficiency in intersomitic regions, dilated vessels in the brain (Aase et al, 2007) Birth Defects Res C Embryo Today. Author manuscript; available in PMC 2009 June 1.…”