Fishing for the signals that pattern the face

Zebrafish are a powerful system for studying the early embryonic events that form the skull and face, as a model for human craniofacial birth defects such as cleft palate. Signaling pathways that pattern the pharyngeal arches (which contain skeletal precursors of the palate, as well as jaws and gills) are discussed in light of a recent paper in BMC Developmental Biology on requirements for Hedgehog signaling in craniofacial development

Plasticity in Zebrafish hox Expression in the Hindbrain and Cranial Neural Crest

AbstractThe anterior–posterior identities of cells in the hindbrain and cranial neural crest are thought to be determined by their Hox gene expression status, but how and when cells become committed to these identities remain unclear. Here we address this in zebrafish by cell transplantation, to test plasticity in hox expression in single cells. We transplanted cells alone, or in small groups, between hindbrain rhombomeres or between the neural crest primordia of pharyngeal arches. We found that transplanted cells regulated hox expression according to their new environments. The degree of plasticity, however, depended on both the timing and the size of the transplant. At later stages transplanted cells were more likely to be irreversibly committed and maintain their hox expression, demonstrating a progressive loss of responsiveness to the environmental signals that specify segmental identities. Individual transplanted cells also showed greater plasticity than those lying within the center of larger groups, suggesting that a community effect normally maintains hox expression within segments. We also raised experimental embryos to larval stages to analyze transplanted cells after differentiation and found that neural crest cells contributed to pharyngeal cartilages appropriate to the anterior–posterior level of the new cellular environment. Thus, consistent with models implicating hox expression in control of segmental identity, plasticity in hox expression correlates with plasticity in final cell fate

A Tale of Three Watersheds: Nonpoint Source Pollution and Conservation Practices across Iowa

Resource /Energy Economics and Policy, Q25,

Requirement for endoderm and FGF3 in ventral head skeleton formation

International audienc

Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch

How does pattern formation occur accurately when confronted with tissue growth and stochastic fluctuations (noise) in gene expression? Dorso-ventral (D-V) patterning of the mandibular arch specifies upper versus lower jaw skeletal elements through a combination of Bone morphogenetic protein (Bmp), Endothelin-1 (Edn1), and Notch signaling, and this system is highly robust. We combine NanoString experiments of early D-V gene expression with live imaging of arch development in zebrafish to construct a computational model of the D-V mandibular patterning network. The model recapitulates published genetic perturbations in arch development. Patterning is most sensitive to changes in Bmp signaling, and the temporal order of gene expression modulates the response of the patterning network to noise. Thus, our integrated systems biology approach reveals non-intuitive features of the complex signaling system crucial for craniofacial development, including novel insights into roles of gene expression timing and stochasticity in signaling and gene regulation

Zebrafish endochondral growth zones as they relate to human bone size, shape and disease

Research on the genetic mechanisms underlying human skeletal development and disease have largely relied on studies in mice. However, recently the zebrafish has emerged as a popular model for skeletal research. Despite anatomical differences such as a lack of long bones in their limbs and no hematopoietic bone marrow, both the cell types in cartilage and bone as well as the genetic pathways that regulate their development are remarkably conserved between teleost fish and humans. Here we review recent studies that highlight this conservation, focusing specifically on the cartilaginous growth zones (GZs) of endochondral bones. GZs can be unidirectional such as the growth plates (GPs) of long bones in tetrapod limbs or bidirectional, such as in the synchondroses of the mammalian skull base. In addition to endochondral growth, GZs play key roles in cartilage maturation and replacement by bone. Recent studies in zebrafish suggest key roles for cartilage polarity in GZ function, surprisingly early establishment of signaling systems that regulate cartilage during embryonic development, and important roles for cartilage proliferation rather than hypertrophy in bone size. Despite anatomical differences, there are now many zebrafish models for human skeletal disorders including mutations in genes that cause defects in cartilage associated with endochondral GZs. These point to conserved developmental mechanisms, some of which operate both in cranial GZs and limb GPs, as well as others that act earlier or in parallel to known GP regulators. Experimental advantages of zebrafish for genetic screens, high resolution live imaging and drug screens, set the stage for many novel insights into causes and potential therapies for human endochondral bone diseases

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

I-BEAT: New ultrasonic method for single bunch measurement of ion energy distribution

The shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens' principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. This novel method, which we refer to as Ion-Bunch Energy Acoustic Tracing (I-BEAT), is a generalization of the ionoacoustic approach. Featuring compactness, simple operation, indestructibility and high dynamic ranges in energy and intensity, I-BEAT is a promising approach to meet the needs of petawatt-class laser-based ion accelerators. With its capability of completely monitoring a single, focused proton bunch with prompt readout it, is expected to have particular impact for experiments and applications using ultrashort ion bunches in high flux regimes. We demonstrate its functionality using it with two laser-driven ion sources for quantitative determination of the kinetic energy distribution of single, focused proton bunches.Comment: Paper: 17 Pages, 3 figures Supplementary Material 16 pages, 7 figure

Aquaporins Have Regional Functions in Development of Refractive Index in the Zebrafish Eye Lens

Purpose: In the eye lens, cytosolic protein concentrations increase progressively from the periphery to the center, contributing to the gradient of refractive index (GRIN). Aquaporins are membrane proteins of lens fiber cells that regulate water transport and adhesion and interact with cytoskeletal proteins. This study investigates how these membrane proteins contribute to proper development of the lens GRIN. Methods: Loss-of-function deletions of aqp0a and/or aqp0b in zebrafish were generated using CRISPR/Cas9 gene editing. Lenses of single aqp0a-/- mutants, single aqp0b-/- mutants, and double aqp0a-/-/aqp0b-/- mutants from larval to elderly adult stages were measured using x-ray Talbot interferometry at SPring8 in Japan. The three-dimensional GRIN profiles in two orthogonal cross-sectional planes of each lens were analyzed and compared with in vivo images and previous results obtained from wild-type lenses. Results: Single aqp0a-/- mutants tended to show asymmetric GRIN profiles, with the central plateau regions shifted anteriorly. Single aqp0b-/- mutants had smooth, symmetric GRIN profiles throughout development until spoke opacities appeared in several extremely old samples. Double aqp0a-/-/aqp0b-/- mutants showed lower magnitude GRIN profiles, as well as dips in the central plateau region. Conclusions: These findings suggest that Aqp0a and Aqp0b have region-specific functions in the lens: Aqp0a is active peripherally, regulating centralization of the plateau region, and this function cannot be compensated for by Aqp0b. In the lens center, either Aqp0a or Aqp0b is required for formation of the plateau region, as well as for the GRIN to reach its maximum magnitude in mature lenses

Hot Quarks and Gluons at an Electron-Ion Collider

The nuclear wave-function is dominated at low- and medium-x by gluons. As the rapid growth of the gluon distribution towards low x, as derived from current theoretical estimates, would violate unitarity, there must be a mechanism that tames this explosive growth. This is most efficiently studied in colliders running in e+A mode, as the nucleus is an efficient amplifier of saturation effects occurring with high gluon densities. In fact, large A can lead to these effects manifesting themselves at energies a few orders of magnitude lower than in e+p collisions. In order to study these effects, there are proposals to build an e+A machine in the USA, operating over a large range of masses and energies. These studies will allow for an in-depth comparison to A+A collisions where results have given tantalising hints of a new state of matter with partonic degrees of freedom. In order to explain these results quantitively, the gluons and their interactions must be understood fully as they are the dominant source of hard probes at both RHIC and LHC energies.Comment: Proceedings of Hot Quarks 2008 - submitted to EPJ