Cytoskeleton and Adhesion in Myogenesis

The function of muscle is to contract, which means to exert force on a substrate. The adaptations required for skeletal muscle differentiation, from a prototypic cell, involve specialization of housekeeping cytoskeletal contracting and supporting systems into crystalline arrays of proteins. Here I discuss the changes that all three cytoskeletal systems (microfilaments, intermediate filaments, and microtubules) undergo through myogenesis. I also discuss their interaction, through the membrane, to extracellular matrix and to other cells, where force will be exerted during contraction. The three cytoskeletal systems are necessary for the muscle cell and must exert complementary roles in the cell. Muscle is a responsive system, where structure and function are integrated: the structural adaptations it undergoes depend on force production. In this way, the muscle cytoskeleton is a portrait of its physiology. I review the cytoskeletal proteins and structures involved in muscle function and focus particularly on their role in myogenesis, the process by which this incredible muscle machine is made. Although the focus is on skeletal muscle, some of the discussion is applicable to cardiac and smooth muscle.

Changes in γ-Tubulin Protein Distribution in Zebrafish (Danio rerio) Oocytes and the Early Cleavage-Stage Embryo

We investigated the distribution of γ-tubulin in zebrafish oocytes and embryos using epifluorescent or confocal microscopy and γ-tubulin antibodies. During meiotic maturation of zebrafish oocytes, γ-tubulin begins redistribution from oocyte ooplasm and cortex to the future blastodisc region at the animal pole. In activated eggs, γ-tubulin was uniformly distributed in the enlarging blastodisc with label emanating from the yolk cell. In newly fertilized eggs, γ-tubulin was evenly distributed in blastomere cytoplasm, with the presence of pronuclei but initially lacking discernable centrosomes. During early cleavage, especially at the eight-cell stage, striking arc-shaped/rings (A/R) of putative centrosomes were detected. Decreasing γ-tubulin was seen in yolk cells while early cleavage blastomeres had strong cytoplasmic label along with obvious A/R arrays. In addition, we found the orientation of the A/R array and nuclear division alternated by about 90 degrees for each cell cycle along with alternation of punctate and A/R arrays.

Thalidomide Embryopathy: An Enigmatic Challenge

Thalidomide remains one of the world’s most notorious drugs due to the severe birth defects it induced in children between 1957 and 1962. Yet, to some this drug is a lifesaver, as it now enjoys renaissance in the treatment for a wide range of conditions including leprosy, multiple myeloma, Behcet’s disease, and some cancers. However, thalidomide has also been linked to causing a new generation of thalidomide survivors in Brazil, where the drug is used to treat leprosy. Surprisingly how thalidomide causes birth defects and how it acts in the treatment of clinical conditions are still far from clear. In the past decade great strides in our understanding of the actions of the drug, as well as molecular targets, have been made. The purpose of this review is to look at the recent work carried out into understanding how thalidomide causes birth defects, it’s molecular targets and the challenges that remain to be elucidated. These challenges include identifying clinically relevant but nonteratogenic forms of the drug, and the mechanisms underlying phocomelia and species specificity.

Gene Networks during Skeletal Myogenesis

Mammalian skeletal muscles are derived from mesoderm segments flanking the embryonic midline. Upon receiving inductive cues from the adjacent neural tube, lateral plate mesoderm, and surface ectoderm, muscle precursors start to delaminate, migrate to their final destinations and proliferate. Muscle precursor cells become committed to the myogenic fate, become differentiated muscle cells, and fuse to form myofibers. Myofibers then fuse together to form the muscle groups. Muscle precursor cells have the ability to proliferate, and differentiate during development, while a subset remains capable of regeneration and repair of local injuries in adulthood. When the process of muscle development is perturbed such as in muscular dystrophies and injuries, ways to intervene and allow for proper muscle development or repair are the focus of regenerative medicine. Thus, understanding the developmental program of muscle at the genetic, cellular, and molecular levels has become a major focus of skeletal muscle regeneration research in the last few years.

DLK1 Protein Expression during Mouse Development Provides New Insights into Its Function

Delta-like 1 homolog (DLK1) is a noncanonical ligand in the Delta-Notch signalling pathway. Although Dlk1 mRNA is abundantly present embryonically and declines rapidly just before birth, Dlk1 knockouts display a relatively mild phenotype. To assess whether this mild phenotype was due to posttranscriptional regulation, we studied the expression of DLK1 protein in mouse embryos and found abundant expression in liver, lung, muscle, vertebrae, pancreas, pituitary, and adrenal gland(s). DLK1 expression was absent in heart, stomach, intestine, kidney, epidermis, and central nervous system. DLK1 protein expression, therefore, correlates well with the reported Dlk1 mRNA expression pattern, which shows that its expression is mainly regulated at the pretranslational level. The comparison of the reported expression patterns of Notch mRNA and those of DLK1 in organs where lineage commitment and branching morphogenesis are important developmental processes suggests that DLK1 is a ligand that prevents premature Notch-dependent differentiation, possibly by competing with canonical ligands.