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PubMed1988

A method for predicting the cranio-caudal position of secondary embryonic structures.

The morphogenetic events that give rise to a specific body pattern have to date avoided extensive elucidation. Extant models of pattern formation have dealt almost exclusively with the "primary patterning" of structures in the embryo. These "universal" models fail to explain many morphological conditions, such as the simultaneous change in position of the limbs, celom, mesonephros, and umbilical artery relative to the somites as a result of a single mutation. In the present paper, we propose that the relation between two non-periodic waves may function to determine the position of "secondary structures", such as the limbs, in the embryo, relative to primary structures such as the somites. We propose that if two morphogenetic events are initiated at different times from the same region of the embryo, and are progressing in a cranio-caudal sequence at different rates, then the location of a given structure along the body axis can be described as a function of the two events. Applications and predictions based on the proposal are presented. Evidence from observations of morphogenetic events in the chick embryo, which tend to support the model, are also presented.

Animals↗
PubMed1984

Body hair growth in women: normal or hirsute.

The distribution and density of terminal hair growth in 19 different body regions in 113 women of fertile age complaining of embarrassing hair growth (group A) are compared with the findings in 100 normal women of comparable age (group B). Apart from three regions the former group demonstrated significantly more frequent and heavier hair growth than the latter. A stepwise discriminant analysis showed that the best separation between the two groups could be obtained by assessing the hair growth in the lip, chin, and public region. With this set of variables, four women from group A were incorrectly classified as belonging to group B and one woman from group B was classified as belonging to group A. The serum concentration of testosterone was significantly higher and the serum concentration of TeBG significantly lower in group A than in group B (P less than 0.001). Menstrual pattern, body weight, and hereditary factors in group A vs. group B support the impression that the increased terminal hair growth found in group A is due to physiological factors. From the present data it can be concluded that appraisal of the facial and public terminal hair growth should in most cases be sufficient for separating possible hirsutism from normal hair growth in women.

Adolescent↗
PubMed1984

Temporal evolution of body surface map patterns following acute inferior myocardial infarction.

We studied the evolution of body-surface potential map (BSPM) patterns in 32 patients following first acute inferior myocardial infarction. Initial BSPMs were obtained at a mean of 79 hours post-infarction; follow-up BSPMs, a mean of eight months post-infarction. Temporal area-of-difference maps, constructed by subtracting initial from follow-up group-mean BSPMs, revealed reciprocal changes over the superior and inferior torso for both Q-zone and ST-segment time-integral distributions. The temporal changes in Q-zone patterns were small but definite: over the inferior torso there was a relative gain in Q-zone values and, over the superior torso, a relative decrease. In contrast, there were marked spatial and quantitative changes of ST-segment distributions during the follow-up period. Over the superior torso, particularly anteriorly, there was a gain in ST-segment values; over the inferior torso, a decrease. With the small temporal changes in Q-zone time-integral distributions, individual Q-zone maps continued to reflect a pattern of inferior myocardial infarction at follow-up. In contrast, the marked temporal changes in ST-segment time-integral distributions resulted in individual map patterns at follow-up that were nearly indistinguishable from normal ST-segment maps. The relatively small changes in depolarization time-integral patterns during the early post-infarction period suggest that the Q-zone patterns of the acute phase of myocardial infarction reflect near-irreversible or completed myocardial damage. The marked normalization of repolarization time-integral patterns during the recovery phase suggests, however, that there are also considerable areas of myocardium-at-risk during the early phase of the infarction process which stabilize with time.

Adult↗
PubMed1987

Animal model: ceroidosis (ceroid-lipofuscinosis) in Australian cattle dogs.

Ceroid-lipofuscinosis is described in Australian Cattle dogs. Lesions included storage of ceroid-lipofuscin in most tissues with characteristic ultrastructural inclusion body patterns in neurons and other cells. Dolichol concentration of the affected dog's brain was similar to those in age-matched control dog brains. However, concentrations in brain, liver and kidneys were markedly higher than in a slightly younger dog. Biochemical data including lysosomal enzyme activities exclude other lysosomal storage diseases. The clinical and pathological features of this disorder resemble those of the juvenile Spielmeyer-Vogt type of Batten disease in humans.

Age Factors↗
PubMed1992

The role of growth factors in embryonic induction in Xenopus laevis.

Establishment of the body pattern in all animals, and especially in vertebrate embryos, depends on cell interactions. During the cleavage and blastula stages in amphibians, signal(s) from the vegetal region induce the equatorial region to become mesoderm. Two types of peptide growth factors have been shown by explant culture experiments to be active in mesoderm induction. First, there are several isoforms of fibroblast growth factor (FGF), including aFGF, bFGF, and hst/kFGF. FGF induces ventral, but not the most dorsal, levels of mesodermal tissue; bFGF and its mRNA, and an FGF receptor and its mRNA, are present in the embryo. Thus, FGF probably has a role in mesoderm induction, but is unlikely to be the sole inducing agent in vivo. Second, members of the transforming growth factor-beta (TGF-beta) family. TGF-beta 2 and TGF-beta 3 are active in induction, but the most powerful inducing factors are the distant relatives of TGF-beta named activin A and activin B, which are capable of inducing all types of mesoderm. An important question relates to the establishment of polarity during the induction of mesoderm. While all regions of the animal hemisphere of frog embryos are competent to respond to activins by mesoderm differentiation, only explants that include cells close to the equator form structures with some organization along dorsoventral and anteroposterior axes. These observations suggest that cells in the blastula animal hemisphere are already polarized to some extent, although inducers are required to make this polarity explicit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The primitive streak.

The emphasis of this review is on the primitive streak of the chick embryo, collated with such information as is available on the mouse embryo. Little modern work has been published on any reptile primitive streak. The following topics are considered: evolutionary significance; formation of the primitive streak; ingression and de-epithelialisation; the basal lamina; migration from the primitive streak of the endoderm and mesoderm; the role of the extracellular matrix; changes in cell adhesiveness; regression of the primitive streak and its role in body patterning; the primitive streak and induction.

Animals↗
PubMed1985

The engrailed locus of Drosophila: structural analysis of an embryonic transcript.

cDNA clones originating from the engrailed gene of Drosophila have been isolated from recombinant phage libraries that were made using poly(A)+ RNA extracted from early embryos. The DNA sequence of one of these clones includes a homeo box, a 180 bp sequence present in several other Drosophila genes important in formation of body pattern during development. The homeo boxes found in the other Drosophila genes, as well as in cognate sequences from a wide range of segmented animals, including higher vertebrates, are highly conserved. By contrast, the homeo box within the engrailed gene diverges substantially and, unlike the other homeo boxes, is interrupted by an intervening sequence. The engrailed homeo box is located near the 3' end of a 1700 bp open reading frame. If translated, this sequence would produce a protein of unusual composition. We also show that a neighboring gene has a large region with strong homology to engrailed, and that it also contains a homeo box.

Amino Acid Sequence↗
PubMed1986

Zygotically active genes that affect the spatial expression of the fushi tarazu segmentation gene during early Drosophila embryogenesis.

The establishment of the segmental body pattern of Drosophila requires the coordinated functions of three classes of zygotically active genes early in development. We have examined the effects of mutations in these genes on the spatial expression of the fushi tarazu (ftz) pair-rule segmentation gene. Mutations in four gap loci and in three pair-rule loci dramatically affect the initial pattern of transverse stripes of ftz-containing nuclei. Five other pair-rule genes and several other loci that affect the larval cuticular pattern do not detectably affect ftz expression. No simple regulatory relationships can be deduced. Rather, expression of the ftz gene depends upon the interactions among the different segmentation genes active at each position along the anterior-posterior axis of the early embryo.

Animals↗
PubMed1989

Structure of the Drosophila BicaudalD protein and its role in localizing the posterior determinant nanos.

Mutations in the BicaudalD (BicD) gene lead to a global reorganization of the Drosophila body pattern such that the head, thoracic, and anterior abdominal segments are replaced by posterior abdominal segments and terminalia. We first provide evidence that the primary cause of this phenotype is the inhibition of two anterior factors, bicoid and hunchback, by mislocalized activity of the posterior determinant nanos. We then describe the isolation of the BicD gene and show that it encodes a coiled-coil protein similar to the carboxy-terminal portion of the myosin heavy chain. Finally, we find that BicD protein is uniformly distributed throughout wild-type oocytes but is concentrated at the anterior pole of BicD mutant oocytes together with ectopic nanos activity. Taken together, these results suggest that BicD encodes a cytoskeleton-like protein involved in transporting or anchoring the nanos morphogen within the oocyte cytoplasm.

Amino Acid Sequence↗
PubMed1991

oskar mRNA is localized to the posterior pole of the Drosophila oocyte.

Mutants of the maternal posterior-group genes of Drosophila lack posterior body pattern elements and germ cells, both of which form through the action of determinants localized to the posterior pole of the oocyte. We report that transcripts of one of these genes, oskar, become localized to the posterior pole of oocytes shortly after the oocyte begins to differentiate visibly. Analysis of various posterior-group mutants reveals that localization of oskar mRNA is an early step in the posterior localization pathway. In addition, we find that nonsense oskar mutations disrupt osk mRNA localization, while missense oskar mutations do not.

Amino Acid Sequence↗
PubMed1992

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals↗
PubMed1992

The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development.

The Drosophila runt gene functions in several developmental pathways during embryogenesis. This gene was initially characterized due to the pivotal role that it plays in the genetic regulatory network that establishes the segmented body pattern. Recently it was found that this X-chromosome-linked gene is one of several dosage-sensitive, X-linked components that is involved in activating the Sex-lethal gene in blastoderm stage female embryos. Finally, this gene is also extensively re-expressed in later stages of embryogenesis in the developing nervous system where it plays an important role in the development of specific neural lineages. We have initiated an analysis of the runt cis-regulatory region in order to investigate runt's roles in these (and other) developmental pathways. Analysis of both the function and the expression patterns of runt genes with truncated cis-regulatory regions indicates that there are multiple elements that make quantitative contributions to runt regulation during segmentation. We find that sequences that are more than 8.5 kb upstream of the runt promoter are necessary for normal expression during the post-blastoderm stages of embryogenesis. Genetic experiments indicate that the post-blastoderm expression of runt is vital to the organism.

Alleles↗
PubMedDate not supplied

Permanent distortion of positional system of Xenopus embryo by brief early perturbation in gravity.

The formation of a body plan from an initially radially symmetrical egg during animal development is presumed to involve a 'positional system'and a subsequent mechanism of local response to position values provided by this system. Early gene products intimately connected with the latter response mechanism have been identified in Drosophila, and because these share conserved sequences with possible counterparts in vertebrates , there is renewed interest in understanding the physiological nature of the positional system itself in a vertebrate embryo. In the frog Xenopus, body position value appears to be specified in outline across much of the egg material by stages comprising a few cells, after only approximately 2h of development. This is already suggestive of a structural or mechanical recording system rather than a diffusion-controlled gradient. I describe here an experiment aimed at perturbing the positional system by causing gravity-driven rearrangements within eggs which conflict with their own, self-organizing rearrangements near the time of the first cleavage. The system appears to retain its full regulatory properties during only a brief time interval, so that records of positional profiles disturbed at the close of that interval are permanent, and give rise to systematically abnormal body patterns in otherwise healthy larvae. The results are inconsistent with the notion that Xenopus primary pattern results from a set of determinant 'plasms' in the egg, or from a mechanism dominated by long-range diffusion of molecules.

Animals↗
PubMedDate not supplied

Maternal control of Drosophila segmentation gene expression.

Several genes have been identified that are involved in establishing the segmented body pattern during development of the fruit-fly Drosophila melanogaster. These fall into several classes on the basis of the kind of alteration to the wild-type segmentation pattern observed in mutant embryos. For example, mutations of the pair-rule class, such as fushi tarazu (ftz), cause the deletion of pattern elements with a two-segment periodicity; those of the gap class, such as knirps, cause the deletion of contiguous groups of segments. The availability of antibodies against the ftz protein has allowed its spatial pattern of expression to be studied during the development of wild-type and mutant embryos. The aim of the latter kind of experiment is to investigate possible interactions between these important genes. We have recently reported that knirps mutations cause a striking alteration to the pattern of transverse stripes of ftz expression usually seen during embryogenesis. Knirps is a zygotically-expressed gene, but recently a class of maternally-active genes has been identified that causes similar defects in pattern formation. We have now investigated the pattern of ftz expression in mutants of this class and have found that while they do have features seen in knirps mutants, they also exhibit significant differences between the different mutations reflecting the distinct but overlapping domains of gene activity. These observations demonstrate that maternally-active segmentation genes regulate zygotic gene expression, and that some of their effects on ftz may be directed through the knirps gene.

Animals↗
PubMed1988

Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps.

The body pattern along the anterior-posterior axis of the insect embryo is thought to be established by two organizing centres localized at the ends of the egg. Genetic analysis of the polarity-organizing centres in Drosophila has identified three distinct classes of maternal effect genes that organize the anterior, posterior and terminal pattern elements of the embryo. The factors provided by these gene classes specify the patterns of expression of the segmentation genes at defined positions along the longitudinal axis of the embryo. The system responsible for organizing the posterior segment pattern is a group of at least seven maternal genes and the zygotic gap gene knirps (kni). Their mutant phenotype has adjacent segments in the abdominal region of the embryo deleted. Genetic analysis and cytoplasmic transplantation experiments suggested that these maternal genes are required to generate a 'posterior activity' that is thought to activate the expression of kni (reviewed in ref. 2). The molecular nature of the members of the posterior group is still unknown. Here we report the molecular characterization of the kni gene that codes for a member of the steroid/thyroid receptor superfamily of proteins which in vertebrates act as ligand-dependent DNA-binding transcription regulators.

Abdomen↗
PubMed1988

cis-acting sequences responsible for anterior localization of bicoid mRNA in Drosophila embryos.

The anterior body pattern of Drosophila melanogaster is specified in large part by the protein product of the bicoid (bcd) gene which functions as a graded morphogen with its peak of expression at the anterior pole of the embryo. Formation of the gradient is dependent on prior localization of bcd messenger RNA at the anterior pole of the egg cell during oogenesis. Here we demonstrate that a discrete portion of the bcd mRNA is necessary for anterior localization of the bcd transcript and is sufficient to cause localization of heterologous transcripts. The sequences responsible for localization appear to span an interval of about 625 base pairs in the 3' untranslated portion of the bcd mRNA and to include regions capable of forming extensive secondary structure. Transcripts from bcd are synthesized predominantly, if not exclusively, in the nurse cells and then transported to the oocyte by connections at the prospective anterior pole. Our findings support the proposal that bcd transcripts are selectively recognized and trapped as they enter the anterior tip of the oocyte, and suggest that this localization process is mediated by anchored sequence-specific receptors in the oocyte cytoplasm.

Animals↗
PubMed1992

Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development.

Amino Acid Sequence↗
PubMed1995

Homeotic genes and the evolution of arthropods and chordates.

Clusters of homeotic genes sculpt the morphology of animal body plans and body parts. Different body patterns may evolve through changes in homeotic gene number, regulation or function. Recent evidence suggests that homeotic gene clusters were duplicated early in vertebrate evolution, but the generation of arthropod and tetrapod diversity has largely involved regulatory changes in the expression of conserved arrays of homeotic genes and the evolution of interactions between homeotic proteins and the genes they regulate.

Animals↗