Jamming by shear

A broad class of disordered materials including foams, glassy molecular systems, colloids and granular materials can form jammed states. A jammed system can resist small stresses without deforming irreversibly, whereas unjammed systems flow under any applied stresses. The broad applicability of the Liu-Nagel jamming concept has attracted intensive theoretical and modelling interest but has prompted less experimental effort. In the Liu-Nagel framework, jammed states of athermal systems exist only above a certain critical density. Although numerical simulations for particles that do not experience friction broadly support this idea, the nature of the jamming transition for frictional grains is less clear. Here we show that jamming of frictional, disk-shaped grains can be induced by the application of shear stress at densities lower than the critical value, at which isotropic (shear-free) jamming occurs. These jammed states have a much richer phenomenology than the isotropic jammed states: for small applied shear stresses, the states are fragile, with a strong force network that percolates only in one direction. A minimum shear stress is needed to create robust, shear-jammed states with a strong force network percolating in all directions. The transitions from unjammed to fragile states and from fragile to shear-jammed states are controlled by the fraction of force-bearing grains. The fractions at which these transitions occur are statistically independent of the density. Jammed states with densities lower than the critical value have an anisotropic fabric (contact network). The minimum anisotropy of shear-jammed states vanishes as the density approaches the critical value from below, in a manner reminiscent of an order-disorder transition.     

Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.     

A transgenic insertion upstream of sox9 is associated with dominant XX sex reversal in the mouse

In most mammals, male development is triggered by the transient expression of the Y-chromosome gene, Sry, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Several genes, in particular Sox9, have a crucial role in this pathway. Despite this, the direct downstream targets of Sry and the nature of the pathway itself remain to be clearly established. We report here a new dominant insertional mutation, Odsex (Ods), in which XX mice carrying a 150-kb deletion (approximately 1 Mb upstream of Sox9) develop as sterile XX males lacking Sry. During embryogenesis, wild-type XX fetal gonads downregulate Sox9 expression, whereas XY and XX Ods/+ fetal gonads upregulate and maintain its expression. We propose that Ods has removed a long-range, gonad-specific regulatory element that mediates the repression of Sox9 expression in XX fetal gonads. This repression would normally be antagonized by Sry protein in XY embryos. Our data are consistent with Sox9 being a direct downstream target of Sry and provide genetic evidence to support a general repressor model of sex determination in mammals.     

The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours

In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine to uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.     

Abnormal sexual development in transgenic mice chronically expressing müllerian inhibiting substance

Müllerian inhibiting substance (MIS), also known as anti-Müllerian hormone, is a glycoprotein normally secreted by the Sertoli cells of the fetal and adult testis and by granulosa cells of the postnatal ovary. The production of MIS in the male fetus brings about the regression of the Müllerian ducts, the anlagen of the uterus, oviducts, and upper vagina. In addition, purified MIS induces the formation of seminiferous cord-like structures in fetal rat ovaries cultured in vitro, suggesting that MIS may influence testicular differentiation. We have produced transgenic mice chronically expressing human MIS under the control of the mouse metallothionein-1 promoter to investigate its role during sexual development. In females, chronic expression led to the inhibition of Müllerian duct differentiation, resulting in a blind vagina and no uterus or oviducts. At birth the ovaries had fewer germ cells than normal; during the next two weeks germ cells were lost and the somatic cells became organized into structures resembling seminiferous tubules. Apparently, these structures degenerate as they are undetectable in adult females. The majority of transgenic males developed normally. But in two lines with the highest levels of MIS expression, some males showed feminization of the external genitalia, impairment of Wolffian duct development, and undescended testes. These results suggest that MIS has several distinct roles in mammalian sexual development.     

Requirement for Wnt3 in vertebrate axis formation.

Several studies have implicated Wnt signalling in primary axis formation during vertebrate embryogenesis, yet no Wnt protein has been shown to be essential for this process. In the mouse, primitive streak formation is the first overt morphological sign of the anterior-posterior axis. Here we show that Wnt3 is expressed before gastrulation in the proximal epiblast of the egg cylinder, then is restricted to the posterior proximal epiblast and its associated visceral endoderm and subsequently to the primitive streak and mesoderm. Wnt3-/- mice develop a normal egg cylinder but do not form a primitive streak, mesoderm or node. The epiblast continues to proliferate in an undifferentiated state that lacks anterior-posterior neural patterning, but anterior visceral endoderm markers are expressed and correctly positioned. Our results suggest that regional patterning of the visceral endoderm is independent of primitive streak formation, but the subsequent establishment of anterior-posterior neural pattern in the ectoderm is dependent on derivatives of the primitive streak. These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse.     

Genetically haploid spermatids are phenotypically diploid

Because chromosomal homologues segregate from one another during meiosis, spermatids are genetically different. Post-meiotic gene expression could lead to gametic differences, some of which might lead to preferential transmission of certain alleles over others. In both insects and mammals, however, all the cells derived from a single spermatogonial cell develop within a common syncytium formed as a result of incomplete cytokinesis at each of the mitotic and meiotic cell divisions. It has been proposed that the intercellular bridges connecting the cells, which are about 1 micron in diameter, permit the sharing of cytoplasmic constituents, thus ensuring the synchronous development of a clone of cells and gametic equivalence between haploid spermatids. By analysing the product of a transgene which is expressed exclusively in post-meiotic germ cells in hemizygous transgenic mice, we have shown that genetically distinct spermatids share the product of the transgene and hence can be phenotypically equivalent.     

Contact force measurements and stress-induced anisotropy in granular materials

Interparticle forces in granular media form an inhomogeneous distribution of filamentary force chains. Understanding such forces and their spatial correlations, specifically in response to forces at the system boundaries, represents a fundamental goal of granular mechanics. The problem is of relevance to civil engineering, geophysics and physics, being important for the understanding of jamming, shear-induced yielding and mechanical response. Here we report measurements of the normal and tangential grain-scale forces inside a two-dimensional system of photoelastic disks that are subject to pure shear and isotropic compression. Various statistical measures show the underlying differences between these two stress states. These differences appear in the distributions of normal forces (which are more rounded for compression than shear), although not in the distributions of tangential forces (which are exponential in both cases). Sheared systems show anisotropy in the distributions of both the contact network and the contact forces. Anisotropy also occurs in the spatial correlations of forces, which provide a quantitative replacement for the idea of force chains. Sheared systems have long-range correlations in the direction of force chains, whereas isotropically compressed systems have short-range correlations regardless of the direction.     

Logarithmic rate dependence of force networks in sheared granular materials

Many models of slow, dense granular flows assume that the internal stresses are independent of the shearing rate. In contrast, logarithmic rate dependence is found in solid-on-solid friction, geological settings and elsewhere. Here we investigate the rate dependence of stress in a slowly sheared two-dimensional system of photoelastic disks, in which we are able to determine forces on the granular scale. We find that the mean (time-averaged) stress displays a logarithmic dependence on the shear rate for plastic (irreversible) deformations. However, there is no perceivable dependence on the driving rate for elastic (reversible) deformations, such as those that occur under moderate repetitive compression. Increasing the shearing rate leads to an increase in the strength of the force network and stress fluctuations. Qualitatively, this behaviour resembles the changes associated with an increase in density. Increases in the shearing rate also lead to qualitative changes in the distributions of stress build-up and relaxation events. If shearing is suddenly stopped, stress relaxations occur with a logarithmic functional form over long timescales. This slow collective relaxation of the stress network provides a mechanism for rate-dependent strengthening.