Insulin-like growth factor receptor 1b is required for zebrafish primordial germ cell migration and survival

AbstractInsulin-like growth factor (IGF) signaling is a critical regulator of somatic growth during fetal and adult development, primarily through its stimulatory effects on cell proliferation and survival. IGF signaling is also required for development of the reproductive system, although its precise role in this regard remains unclear. We have hypothesized that IGF signaling is required for embryonic germline development, which requires the specification and proliferation of primordial germ cells (PGCs) in an extragonadal location, followed by directed migration to the genital ridges. We tested this hypothesis using loss-of-function studies in the zebrafish embryo, which possesses two functional copies of the Type-1 IGF receptor gene (igf1ra, igf1rb). Knockdown of IGF1Rb by morpholino oligonucleotides (MO) results in mismigration and elimination of primordial germ cells (PGCs), resulting in fewer PGCs colonizing the genital ridges. In contrast, knockdown of IGF1Ra has no effect on PGC migration or number despite inducing widespread somatic cell apoptosis. Ablation of both receptors, using combined MO injections or overexpression of a dominant-negative IGF1R, yields embryos with a PGC-deficient phenotype similar to IGF1Rb knockdown. TUNEL analyses revealed that mismigrated PGCs in IGF1Rb-deficient embryos are eliminated by apoptosis; overexpression of an antiapoptotic gene (Bcl2l) rescues ectopic PGCs from apoptosis but fails to rescue migration defects. Lastly, we show that suppression of IGF signaling leads to quantitative changes in the expression of genes encoding CXCL-family chemokine ligands and receptors involved in PGC migration. Collectively, these data suggest a novel role for IGF signaling in early germline development, potentially via cross-talk with chemokine signaling pathways

Emergence of a Dynamic Super-Structural Order Integrating Antiferroelectric and Antiferrodistortive Competing Instabilities in EuTiO3

Microscopic structural instabilities of EuTiO3 single crystal were investigated by synchrotron x-ray diffraction. Antiferrodistortive (AFD) oxygen octahedral rotational order was observed alongside Ti derived antiferroelectric (AFE) distortions. The competition between the two instabilities is reconciled through a cooperatively modulated structure allowing both to coexist. The electric and magnetic field effect on the modulated AFD order shows that the origin of large magnetoelectric coupling is based upon the dynamic equilibrium between the AFD - antiferromagnetic interactions versus the electric polarization - ferromagnetic interactions

Gene duplication and functional divergence of the zebrafish insulin‐like growth factor 1 receptors

Insulin‐like growth factor (IGF) 1 receptor (IGF1R)‐mediated signaling plays key roles in growth, development, and physiology. Recent studies have shown that there are two distinct igf1r genes in zebrafish, termed igf1ra and igf1rb. In this study, we tested the hypothesis that zebrafish igf1ra and igf1rb resulted from a gene duplication event at the igf1r locus and that this has led to their functional divergence. The genomic structures of zebrafish igf1ra and igf1rb were determined and their loci mapped. While zebrafish igf1ra has 21 exons and is located on linkage group (LG) 18, zebrafish igf1rb has 22 exons and mapped to LG 7. There is a strong syntenic relationship between the two zebrafish genes and the human IGF1R gene. Using a MO‐based loss‐of‐function approach, we show that both Igf1ra and Igf1rb are required for zebrafish embryo viability and proper growth and development. Although Igf1ra and Igf1rb demonstrated a large degree of functional overlap with regard to cell differentiation in the developing eye, inner ear, heart, and muscle, they also exhibited functional distinction involving a greater requirement for Igf1rb in spontaneous muscle contractility. These findings suggest that the duplicated zebrafish igf1r genes play largely overlapping but not identical functional roles in early development and provide novel insight into the functional evolution of the IGF1R/insulin receptor gene family.— Schlueter, P. J., Royer, T., Mohamed, H. F., Laser, B., Chan, S. J., Steiner, D. F., Duan, C. Gene duplication and functional divergence of the zebrafish insulin‐like growth factor 1 receptors. FASEB J. 20, E462–E471 (2006)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154460/1/fsb2fj053882fje.pd

Controlling magnetic order and quantum disorder in molecule-based magnets

We investigate the structural and magnetic properties of two molecule-based magnets synthesized from the same starting components. Their different structural motifs promote contrasting exchange pathways and consequently lead to markedly different magnetic ground states. Through examination of their structural and magnetic properties we show that [Cu(pyz)(H2O)(gly)2](ClO4)2 may be considered a quasi-one-dimensional quantum Heisenberg antiferromagnet whereas the related compound [Cu(pyz)(gly)](ClO4), which is formed from dimers of antiferromagnetically interacting Cu2+ spins, remains disordered down to at least 0.03 K in zero field but shows a field-temperature phase diagram reminiscent of that seen in materials showing a Bose-Einstein condensation of magnons

Multiferroicity in an organic charge-transfer salt: Electric-dipole-driven magnetism

Multiferroics, showing simultaneous ordering of electrical and magnetic degrees of freedom, are remarkable materials as seen from both the academic and technological points of view. A prominent mechanism of multiferroicity is the spin-driven ferroelectricity, often found in frustrated antiferromagnets with helical spin order. There, similar to conventional ferroelectrics, the electrical dipoles arise from an off-centre displacement of ions. However, recently a different mechanism, namely purely electronic ferroelectricity, where charge order breaks inversion symmetry, has attracted considerable interest. Here we provide evidence for this exotic type of ferroelectricity, accompanied by antiferromagnetic spin order, in a two-dimensional organic charge-transfer salt, thus representing a new class of multiferroics. Quite unexpectedly for electronic ferroelectrics, dipolar and spin order arise nearly simultaneously. This can be ascribed to the loss of spin frustration induced by the ferroelectric ordering. Hence, here the spin order is driven by the ferroelectricity, in marked contrast to the spin-driven ferroelectricity in helical magnets.Comment: 8 pages, 9 figures (including 4 pages and 6 figures in supplementary information). Version 2 with minor errors corrected (legend of Fig. 3c and definition of vectors e and Q

Comprehensive Gene-Expression Survey Identifies Wif1 as a Modulator of Cardiomyocyte Differentiation

During chicken cardiac development the proepicardium (PE) forms the epicardium (Epi), which contributes to several non-myocardial lineages within the heart. In contrast to Epi-explant cultures, PE explants can differentiate into a cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant cultures and maturing Epi cells, we identified genes specifically associated with differentiation towards either of these lineages and genes that are associated with the Epi-lineage restriction. We found a central role for Wnt signaling in the determination of the different cell lineages. Immunofluorescent staining after recombinant-protein incubation in PE-explant cultures indicated that the early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte differentiation in a similar manner as Wnt stimulation. Concordingly, in the mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1 exposure enhances and attenuates differentiation, respectively. In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis