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The Final Report and recommendations of the Royal Commission into Misconduct in the Banking, Superannuation and Financial Services Industry, led by the Hon Kenneth Hayne AC QC, was published on 4 February 2019. The Commonwealth Government's response: highlighting the actions it will take in respect of all of the recommendations. The report (and the preceding interim report) found widespread misconduct. While the focus was on the financial sector the issues highlighted in the Report have wider application for the management and governance of corporate Australia generally. Primarily the Commission found responsibility for the misconduct rested with boards and senior management.

We suggest that the Commission’s recommendations can be made ‘organisation ready’ if the ethical culture is developed in a way that is consistent with internationally recognized human rights norms. Human rights remove some of the subjective element from ethics and replace it with internationally agreed standards ready to be incorporated into thoughtful governance and corporate decision making processes. We suggest that this model can help build valuable social capital so organisations are seen to be self-regulating ethical conduct beyond governmental controls.

This paper suggests that shareholder class actions founded on a failure of the issuer to comply with the continuous disclosure requirements impose significant and unwarranted costs on the market as a result of the material ‘leakage’ they create in the circle of shareholder wealth. The problem is exacerbated by the aspirational nature of the continuous disclosure requirement and the inherent uncertainty in the form of the rule. It is the ambiguity inherent in the rule that has attracted promoters of shareholder class actions to the provision in numbers that dwarf ASIC’s interest in compliance with the provision. Whilst it is accepted that shareholder class actions founded on the continuous disclosure requirements have the potential to encourage compliance are they the best way to achieve that objective? This paper explores three alternative means to stem the flow of capital caused by continuous disclosure based class action claims: a Market Disclosure Panel, re-introduction of fault elements into shareholder compensation actions or the development of a disclosure judgement rule each of which could be considered in the subsequent work of the Australian Law Reform Commission in its Inquiry into Class Action Proceedings and Third-Party Litigation Funders.

Resumen Introduccion El misoprostol es una analogo de las prostaglandinas E1, actualmente autorizado en nuestro ambito para el tratamiento de la ulcera de estomago y la prevencion de lesiones gastrointestinales inducida por AINE. Pacientes y metodos Mujer gravida 5 (3 partos eutocicos y 1 embarazo ectopico), con 32 semanas de gestacion, acude a urgencias con desorientacion, confusion, dolor abdominal intenso, T. a 41 °C, 83/46 mmHg, 100 lpm. Se objetiva, taquicardia fetal con FCF basal 170 lpm con buena variabilidad y dinamica uterina irregular. La gestante refiere la autoadministracion intravaginal de 4.000 μg misoprostol. Se inicia tratamiento sintomatico con rehidratacion, antitermicos, antibioticos y maduracion fetal. Tras 5 dias de ingreso se produce parto eutocico con recien nacido vivo pretermino. Conclusion La sobredosis y la toxicidad del misoprostol en gestantes durante el tercer trimestre cursa con hipertermia, alteraciones de la consciencia, hipotension, hipertonia uterina y/o polisistolia, llegando incluso a la muerte fetal. No existe antidoto, por lo tanto, el tratamiento es sintomatico.

Fifteen years ago, cell lineage restriction boundaries were discovered in the embryonic vertebrate hindbrain, subdividing it into a series of cell-tight compartments (known as rhombomeres). Compartition, together with segmentally reiterative neuronal architecture and the nested expression of Hox genes, indicates that the hindbrain has a truly metameric organization. This finding initiated a search for compartments in other regions of the developing brain. The results of recent studies have clarified where compartment boundaries exist, have shed light on molecular mechanisms that underlie their formation and have revealed an important function of these boundaries: the positioning and stabilization of local signalling centres.

The earliest step in establishing the complex neuronal networks in the vertebrate brain is the formation of a scaffold of axon tracts. How the formation of the early axon scaffold is controlled at the molecular level is unclear. Forming part of the scaffold, neurons located at the ventral midbrain-forebrain border (MFB) give rise to the medial longitudinal fascicle(mlf) and the posterior commissure (pc). We demonstrate that the homeobox genes Sax1, Six3, Emx2 and Pax6 are expressed in distinct domains in this area, suggesting that the specification of mlf and pc neurons might be controlled by the combinatorial activity of these transcription factors. We have tested this hypothesis by analysing the function of Sax1 in the embryonic chick brain. Gain-of-function experiments with Sax1 result in alterations to the early axon scaffold, most prominently an enlargement of the mlf at the expense of the pc. Ectopic expression of Sax1 also affects the expression of other ventral homeobox genes, particularly Six3 and Emx2. Our results indicate that the specification of neurons forming the early axon scaffold is governed by a homeobox code, thus resembling the mechanism of neuronal specification in the spinal cord.

For the comparative embryologists of the early 20th century, the segment-like bulges that appear transiently during the early stages of vertebrate hindbrain development were both the object of fascination and the subject of vigorous dispute. Conflicting views were held as to the significance of these 'rhombomeres' to brain development and their more general relevance to head evolution. Whether rhombomeres are inconsequential bumps in the embryonic brain or true segments-iterative or metameric units-has only recently been resolved. A number of studies using more modern techniques (such as immunohistochemistry, in situ hybridisation, axonal tracing, single cell labelling, heterotopic and orthotopic grafting, and the manipulation of gene expression by electroporation) have shown that the hindbrain has a truly metameric cellular organisation. The avian embryo has played a particularly prominent role in such studies by virtue of its large size and accessibility, its amenability to microsurgery, and its well-described anatomy. Furthermore, electrophysiological studies, also on avian embryos, have shown that segmentation of the parent neuroepithelium into rhombomeres plays a crucial part in establishing the functional organization of the hindbrain. Segmentation suggests the early allocation of defined sets of precursor cells and is therefore presumed to allow a specific identity for each successive segment to emerge from a common ground plan. This short review will focus on the contribution the avian embryo has made to our understanding of this fly-like region of the vertebrate brain, in respect of its morphology and neuronal architecture, the cellular and molecular mechanisms involved in establishing and maintaining the segments, and the molecular controls of segmental identity.

Wnt signaling is an important component in patterning the early embryo and specifically the neural plate. Studies in Xenopus, mouse, and zebrafish have shown that signaling by members of the Wnt family of secreted signaling factors, their Frizzled receptors and several inhibitors (sFRP1, sFRP2, sFRP3/Frzb1, Crescent/Frzb2, Dkk1, and Cerberus) are involved. However, very little is known about the expression of genes in the Wnt signaling pathway during early anterior neural patterning in chick. We have performed an expression analysis at neural plate stages of several Wnts, Frizzled genes, and Wnt signaling pathway inhibitors using in situ hybridization. The gene expression patterns of these markers are extremely dynamic. We have identified two candidate molecules for anterior patterning of the neural plate, Wnt1 and Wnt8b, which are expressed in the rostral ectoderm at these stages. Further functional studies on the roles of these markers are underway.

In the avian hindbrain, premigratory neural crest cells undergo programmed cell death (apoptosis) in rhombomeres 3 and 5 (r3, r5). Here, we have attempted to analyze the significance of the loss of neural crest cells from these odd-numbered rhombomeres. When apoptosis is prevented in r3 and r5, r3 crest migrate into the first arch and r5 into the third arch. Interestingly, these extra neural crest cells contributed to the formation of ectopic muscle attachment sites that are also found in those species in which r3 and r5 neural crest cells do not undergo apoptosis. Thus, apoptosis in the odd-numbered rhombomeres appears to be an evolutionarily derived mechanism that is required to eliminate r3 and r5 crest migration into first and third arches and thereby remove these muscle attachment sites.

Studies on the genetic basis of rostral–caudal specification, neural induction, and head development require knowledge of the relevant gene expression patterns. Gaps in our understanding of gene expression have led us to examine the detailed spatiotemporal expression patterns of 19 genes implicated in early development, to learn more about their potential role in specifying and patterning early developmental processes leading to head formation. Here, we report the expression patterns of these markers in blastula- and gastrula-stage chick embryos, using whole-mount in situ hybridisation. Nodal, Fgf8, Bmp7, Chordin, Lim1, Hnf3β, Otx2, Goosecoid, Cerberus, Hex, Dickkopf1, and Crescent are all already expressed by the time the egg is laid. When the primitive streak has reached its full length, a later group of genes, including Ganf, Six3, Bmp2, Bmp4, Noggin, Follistatin, and Qin (BF1), begins to be expressed. We reassess current models of early rostral patterning based on the analysis of these dynamic spatiotemporal expression patterns.

The expression domains of genes implicated in forebrain patterning often share borders at specific anteroposterior positions. This observation lies at the heart of the prosomeric model, which proposes that such shared borders coincide with proposed compartment boundaries and that specific combinations of genes expressed within each compartment are responsible for its patterning. Thus, genes such as Emx1, Emx2, Pax6, and qin (Bf1) are seen as being responsible for specifying different regions in the forebrain (diencephalon and telencephalon). However, the early expression of these genes, before the appearance of putative compartment boundaries, has not been characterized. In order to determine whether they have stable expression domains before this stage, we have compared mRNA expression of each of the above genes, relative both to one another and to morphological landmarks, in closely staged chick embryos. We find that, between HH stage 8 and HH stage 13, each of the genes has a dynamic spatial and temporal expression pattern. To test for autonomy of gene expression in the prosencephalon, we grafted tissue from this region to more caudal positions in the neural tube and analyzed for expression of Emx1, Emx2, qin, or Pax6. We find that gene expression is autonomous in prosencephalic tissue from as early as HH stage 8. In the case of Emx1, our data suggest that, from as early stage 8, presumptive telencephalic tissue also is committed to express this gene. We propose that early patterning along the anteroposterior axis of the presumptive telencephalon occurs across a field that is subdivided by different combinations of genes, with some overlapping areas, but without either sharp boundaries or stable interfaces between expression domains.

The diencephalon comprises three functionally distinct regions: synencephalon, dorsal thalamus, and ventral thalamus. Patterning of the diencephalon has been proposed to involve subdivision of its anteroposterior axis into segments, neuromeres or prosomeres (Bergquist and Kallen, 1954; Vaage, 1969; Figdor and Stern, 1993; Rubenstein et al., 1994; Redies et al., 2000; Yoon et al., 2000). However, the number and sequence of diencephalic neuromeres, or even their existence, are uncertain. We have examined the proposed subdivisions by morphology, gene expression, acquisition of boundary-specific phenotypes, and cell lineage restriction. We find that at stage 16 in chick the diencephalon is divided into synencephalon and parencephalon. The synencephalon exhibits neuromeric morphology, expressesProx, and acquires neuromere boundary properties at its interface with both the midbrain and the parencephalon. Although the mesencephalic/synencephalic boundary restricts cell mixing, the synencephalic/parencephalic boundary does not. Similarly, there is no lineage restriction between the parencephalon and the more rostral forebrain (secondary prosencephalon). Subdivision of the parencephalon into ventral and dorsal thalamus involves the formation of a narrow intraparencephalic territory, the zona limitans intrathalamica (zli). This is correlated with the acquisition of cell lineage restriction at both anterior and posterior borders of the zli, the appearance of boundary-specific properties, and Gbx2 and Dlx2 expression in dorsal thalamic and ventral thalamic territories, respectively. At stage 22, the synencephalon is divided into two domains, distinguished by differential gene expression and tissue morphology, but associated with neither a boundary phenotype nor cell lineage restriction. Our results suggest that the diencephalon does not have an overt segmental pattern.

The putative transcription factor Lbx1 is expressed in the mantle zone of the hindbrain and spinal cord caudal to rhombomere 1, in a specific domain of the alar plate. The Lbx1 domain overlaps with the expression domains for Tlx3 and partially with the domains for Pax2/Lim1. The ventral border of the Lbx1 domain coincides with the ventral border of the dorsalmost Serrate1 stripe in the ventricular zone. The latter borders the intermediate stripe of both Delta and Lunatic fringe expression. The Lbx1 domain contains differentiated interneurons that project into the lateral longitudinal fasciculus.

Segmentation is a mechanism that controls spatial organization along the anteroposterior axis of the neural tube and is particularly well characterized for the hindbrain region [1]. The generation of distinct and regionally specific structures from each rhombomere is achieved with the almost complete absence of cell mixing between neighboring rhombomeres [2, 3]. Here, we have examined cell mingling at the isthmus, where Otx2-expressing midbrain cells abut Gbx2-expressing hindbrain cells [4]. The sharp line of demarcation between the two expression domains suggests that this interface would be a compartment boundary, with no intermixing of cells, but this has not been directly tested. We have used short-term reaggregation assays to compare the adhesive properties of cells derived from midbrain and anterior hindbrain and cell labeling in vivo directly to monitor cell behavior at the midbrain/hindbrain boundary. Interestingly, our data demonstrate that, in contrast to the rhombomeres, differential adhesion does not seem to operate between the midbrain and anterior hindbrain and that cells move between the two territories. We conclude that these two subdivisions are not maintained by cell lineage restriction but by cells maintaining labile fates.

We describe a simple method of chick whole-embryo culture, which uses a filter paper carrier to hold the early blastoderm and vitelline membranes under tension while the embryo grows on a substratum of agar-albumen. This is a quick and efficient means of setting up cultures of chick embryos beginning at pre-primitive streak stages to stage 10 (stages X--XIV, Eyal-Giladi and Kochav [1976] Dev Biol 49:321-337; stages 1--10, Hamburger and Hamilton [1951] J Morphol 88:49--92). This is an improvement on the original method of New, which used a glass ring and watch glass (New [1955] Exp Morphol 3:320--331). Our modification of New's method, which we call EC (Early Chick, pronounced EASY) culture, facilitates several manipulations in early chick embryos, including microsurgery, grafting, bead implantation, microinjection, and electroporation. Using the EC method, embryos at stage 8 and older can be readily cultured either dorsal-side up (in contrast to New's method) or ventral-side up, as desired; embryos younger than stage 8 can be culture only ventral-side up (as with New's method). We also discuss some alternative methods for setting up these cultures.

The paired box containing transcription factor Pax3 is a crucial regulator of dermomyotome and muscle development. However, the allelic series of Pax3/Splotch mutants also displays characteristic vertebral column malformations, which do not result from defective dorsoventral somite pattern. Rather, vertebral column and sclerotomal phenotypes are reminiscent of the phenotypes observed in the segmentation/somitogenesis mutants rachiterata and pudgy. Moreover, rostrocaudal somite pattern and somitic boundaries are disturbed in Splotch as monitored by the expression of Uncx4.1 and Lunatic fringe. Alterations in EphA4, Dll1, and Uncx4.1 expression are evident already in the condensing paraxial mesoderm, correlating with the first phase of Pax3 expression before and during somite formation. This finding suggests an early function of Pax3 during the formation of epithelial somites.

Here we describe the expression pattern of GATA-2 in the developing chick hindbrain. We found that during the early period of neurogenesis this gene specifically labels a particular neuronal subtype, the contralateral vestibular-acoustic neurons of rhombomere 4, and that expression of this gene in these cells is transient. We also found that GATA-2 labels a broader territory of the ventral neural tube at later stages. As well as this hindbrain expression, we also describe expression of GATA-2 in the otic vesicle, oculomotor nucleus, third nerve and metanephros.

Hypaxial skeletal muscles develop from migratory and non-migratory precursor cells that are generated by the lateral lip of the dermomyotome. Previous work shows that the formation of migratory precursors requires the c-Met and SF/HGF genes. We show here that in mice lacking c-Met or SF/HGF, the initial development of the dermomyotome proceeds appropriately and growth and survival of cells in the dermomyotome are not affected. Migratory precursors are also correctly specified, as monitored by the expression of Lbx1. However, these cells remain aggregated and fail to take up long range migration. We conclude that parallel but independent cues converge on the migratory hypaxial precursors in the dermomyotomal lip after they are laid down: a signal given by SF/HGF that controls the emigration of the precursors, and an as yet unidentified signal that controls Lbx1. SF/HGF and c-Met act in a paracrine manner to control emigration, and migratory cells only dissociate from somites located close to SF/HGF-expressing cells. During long range migration, prolonged receptor-ligand-interaction appears to be required, as SF/HGF is expressed both along the routes and at the target sites of migratory myogenic progenitors. Mice that lack c-Met die during the second part of gestation due to a placental defect. Rescue of the placental defect by aggregation of tetraploid (wild type) and diploid (c-Met−/−) morulae allows development of c-Met mutant animals to term. They lack muscle groups that derive from migratory precursor cells, but display otherwise normal skeletal musculature.

Recent evidence suggests that in vertebrates the formation of distinct neuronal cell types is controlled by specific families of homeodomain transcription factors. Furthermore, the expression domains of a number of these genes correlates with functionally integrated neuronal populations. We have isolated two members of the divergent T-cell leukemia translocation (HOX11/Tlx) homeobox gene family from chick,Tlx-1andTlx-3,and show that they are expressed in differentiating neurons of both the peripheral and central nervous systems. In the peripheral nervous system,Tlx-1andTlx-3are expressed in overlapping domains within the placodally derived components of a number of cranial sensory ganglia.Tlx-3, unlikeTlx-1, is also expressed in neural crest-derived dorsal root and sympathetic ganglia. In the CNS, both genes are expressed in longitudinal columns of neurons at specific dorsoventral levels of the hindbrain. Each column has distinct anterior and/or posterior limits that respect inter-rhombomeric boundaries.Tlx-3is also expressed in D2 and D3 neurons of the spinal cord.Tlx-1andTlx-3expression patterns within the peripheral and central nervous systems suggest that Tlx proteins may be involved not only in the differentiation and/or survival of specific neuronal populations but also in the establishment of neuronal circuitry. Furthermore, by analogy with the LIM genes, Tlx family members potentially define sensory columns early within the developing hindbrain in a combinatorial manner.

There is evidence that oligodendrocytes in the spinal cord are derived from a restricted part of the ventricular zone near the floor plate. An alternative view is that oligodendrocytes are generated from all parts of the ventricular zone. We reinvestigated glial origins by constructing chick–quail chimeras in which dorsal or ventral segments of the embryonic chick neural tube were replaced with equivalent segments of quail neural tube. Ventral grafts gave rise to both oligodendrocytes and astrocytes. In contrast, dorsal grafts produced astrocytes but not oligodendrocytes. In mixed cultures of ventral and dorsal cells, only ventral cells generated oligodendrocytes, whereas both ventral and dorsal cells generated astrocytes. Therefore, oligodendrocytes are derived specifically from ventral neuroepithelium, and astrocytes from both dorsal and ventral.

The most profound feature of the mature vertebrate somite is its organisation into dorsal dermomyotome, intermediate myotome and ventral sclerotome. We analysed the role of potential signalling structures in this dorsoventral pattern by ablating them or transplanting them to ectopic locations in chick embryos. Our data suggest that the somite represents a naïve tissue, entirely depending on external cues for its dorsoventral organisation. Dorsalisation by signals from dorsal neural tube and surface ectoderm stimulates the development of the dermomyotome. Likewise, signals from notochord and floor plate ventralise the somite, at high levels overriding any dorsal information and inducing the sclerotome. The dorsalising factors and lower levels of the ventralising factors act in concert to induce the myotome. Finally, the paraxial mesoderm intrinsically controls its competence to respond to the external inducers.

Expression and mutation analyses in mice suggest that the homeobox-containing gene Engrailed (En) plays a role in dorsoventral patterning of the limb. During the initial stages of limb bud outgrowth, En-1 mRNA and protein are uniformly distributed throughout the ventral limb bud ectoderm. Limbs of En-1−/− mice display a double dorsal phenotype suggesting that normal expression of En-1 in the ventral ectoderm is required to establish and/or maintain ventral limb characteristics. Loss of En-1 function also results in ventral expansion of the apical ectodermal ridge (AER), suggesting that En-1 is also required for proper formation of the AER. To further investigate the role En plays in dorsoventral patterning and AER formation, we have used the replication competent retroviral vector, RCAS, to mis-express mouse En-1 in the early chick limb bud. We show that ectopic En-1 expression in dorsal ectoderm is sufficient to repress the endogenous expression of the dorsal ectodermal marker Wnt7a, with a resultant decrease in Lmx1 expression in underlying dorsal mesenchyme. Furthermore, the AER is disrupted morphologically and the expression patterns of the AER signalling molecules Fgf-8 and Fgf-4 are altered. Consistent with recent evidence that there is a reciprocal interaction between signalling molecules in the dorsal ectoderm, AER, and zone of polarising activity (ZPA), loss of Wnt7a, Fgf-8 and Fgf-4 expression leads to a decrease in expression of the signalling molecule Shh in the ZPA. These results strongly support the idea that, in its normal domain of expression, En-1 represses Wnt7a-mediated dorsal differentiation by limiting the expression of Wnt7a to the dorsal ectoderm. Furthermore, our results provide additional evidence that En-1 is involved in AER formation and suggest that En-1 may act to define ventral ectodermal identity.

Neurotrophins signal through members of the trk family of tyrosine kinase receptors and are known to regulate several neuronal properties. Although initially characterized by their ability to prevent naturally occurring cell death of subsets of neurons during development, neurotrophins can also regulate the proliferation and differentiation of precursor cells. Here we report a novel involvement of neurotrophins in early development of the neural tube. We demonstrate that a functional trkB receptor is expressed by motor neuron progenitors in the ventral neural tube and that treatment of ventral neural tube explants with the trkB ligand Brain-Derived Neurotrophic Factor (BDNF) leads to a significant increase in the number of motor neurons. The only BDNF expression detectable at this stage is by a subset of ventrally projecting interneurons in the dorsal neural tube; ablating this region in vivo leads to a reduction of motor neuron numbers. This loss can be prevented by simultaneous treatment with BDNF. We propose that BDNF produced by dorsal interneurons stimulates proliferation and/or differentiation of motor neuron progenitors after anterograde axonal transport and release in proximity to the trkB-expressing motor neuron precursors, thereby coordinating development between dorsal and ventral regions of the neural tube.

The developing hindbrain is transiently subdivided into structural repeat units, rhombomeres, whose formation is matched by both differential regulatory gene expression and a metameric pattern of early neuronal differentiation and axogenesis. Individual rhombomeres are polyclonal cell lineage restriction units; once defined by transverse interrhombomere interfaces, cells are confined within the territory of a single rhombomere. In order to assess the relevance of this restriction to hindbrain development. It is necessary to understand the underlying mechanism. One possibility is that cells of adjacent rhombomeres acquire differential affinities or adhesive properties. To explore this possibility, we isolated rhombomere cells, mixed them together in short-term aggregation cultures, and assessed the composition of the resulting aggregates. We found that rhombomeres do differ in their affinity: cells from even-numbered rhombomeres sort out from cells of odd-numbered rhombomeres. They also segregate from cells of other even-numbered rhombomeres but to a much lesser extent. This selective cell affinity operates from the time of rhombomere formation until late stages in development. The region-specific segregation was abolished when Ca(2+)-dependent adhesion molecules were inactivated but not when Ca(2+)-independent adhesion molecules were inactivated. These findings suggest that distinct cell affinity restricts cell mixing between adjacent rhombomeres and may be involved in establishing the series of discrete compartments, thereby maintaining anteroposterior positional information during hindbrain development. These results support a general role for cell adhesion molecules in subdividing CNS territories.