Hox Genes as Synchronized Temporal Regulators: Implications for Morphological Innovation

Abstract In vertebrates, clusters of Hox genes express in a nested and hierarchical fashion to endow the embryo’s segments with discrete identities. Later in development, members of the same gene family are employed again to pattern the limb, intestinal, and reproductive systems. A careful analysis of the morphologies of Hox mutant mice suggests that the genes provide qualitatively different cues during the specification of segments than they do during the development of more recently derived structures. In addition to the regulatory differences noted by others, the activity of Hox genes during specification of the vertebrate metameres in some recent deletion experiments is inconsistent with a role for them as strictly spatial determinants. On the contrary, the phenotypes observed are suggestive of a role for them as elements of a generic time-keeping mechanism. By contrast, the specification of more recent evolutionary structures appears to be more spatial andgene-specific. These differences in role and effect may suggest some simple mechanisms by which the Hox clusters operate, and rules by which gene networks can be diverted to create new structures over the course of evolution. Specific predictions and experiments are proposed

Transformations in null mutants of Hox genes: do they represent intercalary regenerates?

In the minds of many, Hox gene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero-posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror-image duplications; and the development of anomalies outside the established domains of normal Hox gene expression. In this paper, Hox gene disruptions are shown to elicit regeneration-like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps of Hox-mediated patterning occurs in Hensen\u27s node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero-posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role of Hox genes in the establishment of segmental identity. In the minds of many, Hox gene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero-posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror-image duplications; and the development of anomalies outside the established domains of normal Hox gene expression. In this paper, Hox gene disruptions are shown to elicit regeneration-like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps of Hox-mediated patterning occurs in Hensen\u27s node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero-posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role of Hox genes in the establishment of segmental identity

Evolution and Emergence: a Re-Evaluation of the New Synthesis

The modern obsession with methodological reductionism in some areas of biology is arguably a product of the exquisitely precise tools now available to dissect problems. Reductionist approaches assume that an understanding of atomized parts will be sufficient to approximate an understanding of the whole. Ironically, the sheer success of this approach and the consequent volume of data generated, particularly as a result of the genome projects, has made comprehension of the larger picture problematic. Consequently, historical patterns of more phenomenologically oriented analyses are re-emerging. This impulse is not new: Gould and Lewontin (1979) argued for a less reductionist view of evolution. They argue that an intense focus upon individual traits risks confusing evolutionary selection with the indirect consequences of other architectural decisions. They also argued that the “baggage” of ancestral traits constrains future possibilities for profound change. The “New Synthesis”, a more recent convergence of paleontology, evolutionary biology, genome science, and embryology provides fertile ground for their critique. New approaches to genome analysis and gene categorization have shown that profound inter-species similarities underlie a generic and robust body plan upon which variant morphologies are built. Moreover, phenomenologically oriented approaches have recently revealed functional and organizational similarities among diverse genomes that are indicative of large and preserved gene regulatory behaviours: genomes appear to be organized into similar regulatory blocks irrespective of species. The implications of these recent discoveries suggest that emergent organizational and functional properties of genomes could impose big constraints upon morphological innovation. They might also explain some of the curious and profound examples of convergent evolution that puzzled Darwin

Captains Contentious: The Dysfunctional Sons of the Brine,

“Honor,” as Douglass Adair explains in Fame and Founding Fathers (1974), “is an ethic of competition, of struggle for eminence and distinction.” “In a partic- ular culture,” he writes, “a sense of honor—a sense of due self-esteem, of proper pride, of dignity appropriate to his station—acts like conscience for a practicing Christian.” Adair argues that “the lust for the psychic reward of fame, honor, and glory, after 1776 becomes a key ingredient in the behavior of Wash- ington and his greatest contemporar- ies.” Gregory D. Massey observes in John Laurens and the American Revolu- tions (2000), “Like his fellow officers, [Continental Army colonel John] Laurens valued his honor or reputation above all else

An Analysis of Operating Environment & Strategy: A Case Study of Tata Motor

This report provides an in-depth study of the environment in which India-based company Tata Motors competes. In order to understand key aspects of the company, a SWOT analysis was conducted to better determine both the internal and external aspects of the operating environment. Using this analysis in combination with a summary of the conditions in the domestic environment, suggested strategies are given. The purpose of these strategies is to provide creative, beneficial, and resourceful ways Tata can continue to succeed in the highly competitive automobile industry. Along with the general strategies, a brief implementation plan is given to demonstrate how to put these strategies into action

Heredity in the Epigenetic Era: Are We Facing a Politics of Reproductive Obligations?

Recent research in the emerging field of epigenetics has implications with the potential to re-ignite acrimony in the discourse of reproductive rights, medical ethics, and the role of the state in our homes and in our lives. For scientists, epigenetics has profoundly realigned our understanding of heredity: epigenetics provides a mechanism through which the environmental challenges met in one generation can be inscribed and transmitted to future offspring. Although both genetic parents have the potential to transmit heritable epigenetic changes to their offspring, mothers have a particularly potent effect because nutrition in the uterine environment can exert a supplemental effect upon the epigenetic imprint of her offspring, and potentially, upon subsequent generations. Moreover, parental care post partum may have generational consequences that are more than just social. Unless discussants have a nuanced understanding of basic epigenetics, women could suffer a disproportionate burden of the obligation to promote fetal, neonatal, and trans-generational health. Drawing upon past patterns of discourse, ethics, and legislation in reproductive rights, I will briefly list some of the challenges and temptations that we will be facing at the individual, familial, social, and legislative levels

More than Rum, Buggery, and the Lash : Social History in American Naval Documents

This essay, however, charts a course to some neglected aspects of the social history of the American sailing navy and urges social historians to cruise in less frequented seas. These aspects include: women; hygiene; patronage of officers toward warrant and petty officers and ratings; and the life-course of warrant and petty officers

Effects of localized application of retinoic acid on Xenopus laevis development

In order to more accurately determine the mechanism by which retinoic acid causes embryonic defects, we have developed a simple method of locally applying retinoic acid rather than immersing the whole embryo in retinoic acid solutions. Retinoic acid was suspended in corn oil and then injected between the surface and the deep ectodermal layers of an early gastrula Xenopus embryo. When droplets containing retinoic acid were injected into the presumptive head region, the embryos exhibited inhibited development of anterior structures near the injection site. Development of the eye, cement gland, hatching gland, olfactory pits, and expression of engrailed protein were all disrupted near the injection site. Inhibited development of anterior structures was far greater on the injected side of the embryo than on the uninjected side. The retinoic acid droplet did not cause an anterior shift of structures on the injected side relative to the uninjected side. These experiments suggest that retinoic acid does not cause global respecification of axial level in the head, but rather suppresses development of anterior structures. Retinoic acid injected into presumptive trunk regions had no discernible effect

Developmental biology: an array of new possibilities

Microarrays offer biologists comprehensive and powerful tools to analyze the involvement of genes in developmental processes at an unprecedented scale. Microarrays that employ defined sequences will permit us to elucidate genetic relationships and responses, while those that employ undefined DNA sequences (ESTs, cDNA, or genomic libraries) will help us to discover new genes, relate them to documented gene networks, and examine the way in which genes (and the process that they themselves control) are regulated. With access to broad new avenues of research come strategic and logistical headaches, most of which are embodied in the reams of data that are created over the course of an experiment. The solutions to these problems have provided interesting computational tools, which will allow us to compile huge data sets and to construct a genome-wide view of development. We are on the threshold of a new vista of possibilities where we might consider in comprehensive and yet specific detail, for example, the degree to which diverse organisms utilize similar genetic networks to achieve similar ends. (C) 2002 Elsevier Science Inc. All rights reserved

Author Correction: Task-dependent representations of stimulus and choice in mouse parietal cortex.

In the original version of this Article, the Acknowledgements section was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article