In vertebrates, hematopoietic and vascular progenitors develop from ventral mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood cells, whereas progenitor cells of subsequent definitive waves form all hematopoietic cell lineages. In this report we examine the development of hematopoietic and vasculogenic cells in normal zebrafish and characterize defects in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study. Expression of these genes identifies embryonic regions that contain hematopoietic and vascular progenitor cells. The expression of c-myb also identifies definitive hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is not required for primitive erythropoiesis in zebrafish even though it is expressed in these cells. Both cloche and spadetail mutant embryos have defects in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs.
The segmentation clock is an oscillating genetic network thought to govern the rhythmic and sequential subdivision of the elongating body axis of the vertebrate embryo into somites: the precursors of the segmented vertebral column. Understanding how the rhythmic signal arises, how it achieves precision and how it patterns the embryo remain challenging issues. Recent work has provided evidence of how the period of the segmentation clock is regulated and how this affects the anatomy of the embryo. The ongoing development of realtime clock reporters and mathematical models promise novel insight into the dynamic behavior of the clock.Key words: Gradient, Modeling, Negative feedback, Oscillator, Signaling, Somitogenesis IntroductionThe segmented anatomy of the vertebrate embryo is evident in the two bilaterally symmetrical rows of somites that flank the notochord along the body axis. These blocks of mesodermal cells give rise primarily to bone, muscle and skin of the adult body, which is correspondingly segmented. Somitogenesis is a rhythmic and sequential process in which each successive bilateral somite pair segregates at a regular time interval from the anterior end of the pre-somitic mesoderm (PSM, see Glossary, Box 1) as the body axis elongates (Fig. 1A,B). Somitogenesis has long been of interest to developmental biologists because it involves the coordination of patterning and growth of a tissue by a regularly repeated morphogenetic process. The topic of this review is the molecular segmentation clock that underlies this periodicity. The segmentation clock has attracted the attention of those interested in biological clocks and the molecular mechanisms of developmental timing, as well as those studying the function and stability of rapidly acting genetic circuits, and the interplay between the properties of single cells and their collective behavior at the tissue level. Finally, the rhythmic nature of the process is the seed for a theoretical interest in somitogenesis that is decades old and now promises a powerful synthesis of experiment and theory that is emblematic of modern embryology.This review first provides an overview of somitogenesis, then describes the prevailing dynamic model for somitogenesis, the Clock and Wavefront mechanism, its molecular phenomenology Development 139, 625-639 (2012) REVIEW Box 1. GlossaryBiological oscillator. A system that generates a periodic variation in the state of a cell, tissue or organism. The vibrating stereocillia bundles of inner ear hair cells, the contraction cycle of cardiac muscle cells, circadian clocks and rhythmic neuronal circuits are all biological oscillators. Coupling. Communication between neighboring oscillators that leads to mutual adjustment of their frequencies. For example, activation of Notch receptors in a presomitic mesoderm cell by Delta from neighboring cells can affect the dynamics of Notch pathway components in the target cell. Frequency profile. Dependence of the frequency of the oscillators in an array on their position. In the segmentat...
When cells move using integrin-based focal adhesions, they pull in the direction of motion with large, ∼100 Pa, stresses that contract the substrate. Integrin-mediated adhesions, however, are not required for in vivo confined migration. During focal adhesion-free migration, the transmission of propelling forces, and their magnitude and orientation, are not understood. Here, we combine theory and experiments to investigate the forces involved in adhesion-free migration. Using a non-adherent blebbing cell line as a model, we show that actin cortex flows drive cell movement through nonspecific substrate friction. Strikingly, the forces propelling the cell forward are several orders of magnitude lower than during focal-adhesion-based motility. Moreover, the force distribution in adhesion-free migration is inverted: it acts to expand, rather than contract, the substrate in the direction of motion. This fundamentally different mode of force transmission may have implications for cell-cell and cell-substrate interactions during migration in vivo.
We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated "bystander" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.
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