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[Pattern formation in Drosophila].

Drosophila proved an excellent system to study molecular processes in establishing the body pattern of an embryo. Genes which are active during oogenesis provide localized cues which regulate a cascade of zygotic genes that determines the developmental fate of the blastoderm cells along the longitudinal axis of the embryo.

Animals

Xenopus mesoderm induction: evidence for early size control and partial autonomy for pattern development by onset of gastrulation.

Experiments are described that examine the state of organisation of the presumptive mesoderm and ectoderm of the Xenopus embryo at stages up to the onset of gastrulation. It is shown that a process during blastula stages, establishing the normal proportions in which this cell population is partitioned to found the two outer 'germ layers', has a positive regulative property. An operation has been performed to excise the yolky endodermal core, at the beginning of gastrulation, leaving only the presumptive territories of mesoderm, neural tissue, epidermis and supra-blastoporal endoderm. This reveals that by this time a stable capacity exists within the induced tissue to express the craniocaudal sequence of the normal pattern, including the proper numbers of somite segments. The mediolateral organisation of such body patterns is however abnormal. The relevance of the observations to understanding mechanisms of axial pattern control is discussed.

Animals

[Growth curves of body weight and their relationship to sexual maturity in laboratory-bred male African green monkeys (Cercopithecus aethiops)].

Nonlinear growth models having a three- or four-parameter family were applied to individual body weight data of 5 male African green monkeys for estimating their growth patterns. Body weight was measured from birth to six years of age and 58 to 114 data items per monkey were collected. The average body weight at birth was 360g with the standard deviation of +/- 25g, 4.54 +/- 0.29 kg at five years of age, and 4.50 +/- 0.12 kg at six years of age at which point body weight was judged to have reached a plateau. Five growth models (Gompertz, Logistic, Richards, Bertalanffy and Brody) were applied to the growth data in this study. As a result, two (Gompertz and Logistic) of the five models were found applicable to all data from the five monkeys. However, the coefficient of determination (R2) obtained by application of the two models were not so large (0.919 +/- 0.05 in Gompertz, 0.889 +/- 0.01 in Logistic). Therefore the data were divided into two groups according to monkey age: the first group being from monkeys between birth and 2 years 10 months of age and the second group was from monkeys older than 2 years 10 months of age. The Gompertz model fitted best the data of the first group in four of the five animals (R2 = 0.982 +/- 0.011). The age at the inflexion point in the Gompertz model nearly corresponded to the age of weaning. The Logistic model was most suitable for the date of the second group in all five animals (R2 = 0.955 +/- 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The genetic basis for piebald patterns in cattle.

Evidence is given for the existence of a dominant mutant, Bl, found in Simmental and some other breeds of cattle that is responsible for white facial pattern. This mutant is independent of the mutant responsible for the typical white facial and body pattern of the Hereford breed. Also, evidence is presented to support a multiple allelic series composed of SH (Hereford pattern), SCS (color-side pattern), S+ (non-spotted wild type), and s (recessive spotting pattern). Alleles SH and SCS are codominant to each other and incompletely dominant over S+, SH, SCS, and S+; all appear to be completely dominant over s. The Dutch belted pattern is probably controlled by an independent dominant mutant, Bt.

Animals

Two gap genes mediate maternal terminal pattern information in Drosophila.

In Drosophila three maternal pattern organizing activities, the anterior, the posterior, and the terminal, establish the anterior-posterior body pattern of the embryo by initiating the spatially restricted activities of the gap class of zygotic segmentation genes. The activities of tailless (tll) and the newly identified gap gene huckebein (hkb) are specifically involved in mediating the maternal terminal information at the posterior end of the blastoderm embryo.

Animals

Probable mechanism for the loss of Barr body in human female tumor with special reference to breast cancer.

One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells. For example, Sohval and Gains (3) reported an absence of the characteristic Barr body pattern of 19 of the 27 teratomas from females and Moore and Barr (4) observed significant variation in Barr body counts in breast cancer cells. Furthermore, a good correlation was made between the frequency of Barr body and prognosis (5,6,7,8,9). From a retrospective study, it was shown that tumours with low Barr body frequency (BBF) had a significant correlation with blood vessel invasion (BVI) and poor prognosis (10). But the reason why patients with low BBF in the tumor with BVI get early recurrence is not known. In this paper an attempt has been made to suggest a mechanism which may be involved in reducing the BBF with high malignant potentiality.

Breast Neoplasms

Graded requirement for the zygotic terminal gene, tailless, in the brain and tail region of the Drosophila embryo.

We have used hypomorphic and null tailless (tll) alleles to carry out a detailed analysis of the effects of the lack of tll gene activity on anterior and posterior regions of the embryo. The arrangement of tll alleles into a continuous series clarifies the relationship between the anterior and posterior functions of the tll gene and indicates that there is a graded sensitivity of anterior and posterior structures to a decrease in tll gene activity. With the deletion of both anterior and posterior pattern domains in tll null embryos, there is a poleward expansion of the remaining pattern. Using anti-horseradish peroxidase staining, we show that the formation of the embryonic brain requires tll. A phenotypic and genetic study of other pattern mutants places the tll gene within the hierarchy of maternal and zygotic genes required for the formation of the normal body pattern. Analysis of mutants doubly deficient in tll and maternal terminal genes is consistent with the idea that these genes act together in a common pathway to establish the domains at opposite ends of the embryo. We propose that tll establishes anterior and posterior subdomains (acron and tail regions, respectively) within the larger pattern regions affected by the maternal terminal genes.

Alleles

Thermographical investigation of decubitus ulcers.

1. Posterior body reference thermograms indicate that in general a similar thermal body pattern of humans does exist. 2. The buttocks, hips, and thighs of a nude subject are thermally cool regions, possibly indicating poor vascular circulation and/or large fat concentrations. 3. Thermograms of the same anatomical area on the same subject under controlled environmental conditions are thermally similar. 4. The scapular region is from 1 to 2 deg F hotter than the sacral region for subjects reclining on Mylar. 5. The 1 deg temperature differential thermograms and the reference thermogram while the subject is on Mylar, in many ways, denote the geometrical shape of the underlying bone structure, especially the bones of the scapulae and sacrum. 6. On the degree temperatue differential thermograms, the anatomical regions most accused of being decubitus ulcer prone are the regions of highest temperatures: the scapulae, sacrum, elbows, and calves. 7. During reactive hyperemia, the visible red flare over the sacrum and coccyx becomes very intense in the first few minutes and then gradually diminishes. The thermal flare persists longer than the visible flare. The extended duration of the thermal flare over the visible red flare is attributed to a continued local elevated metabolic tissue rate caused by the previous engorgement of blood. 8. The thermal mottling seen in the first minute after releasing the load is believed to have been caused by the rapid infusion of blood and the dilation of affected vessels responsible for making up the blood flow debt which occurred during the period of ischemia. 9. A posterior body heating effect noticed immediately after the subject left the Mylar film has been attributed to the insulative qualities of the film. The cooling effect is more difficult to explain, but it is thought that the higher than average room temperature caused an increased evaporative cooling rate response of the two subjects either before getting off the film or immediately after getting off and therefore reduced the temperature of the skin. 10. The maximum reactive hyperemic temperature difference, the difference between the initial standing reference thermogram and the maximum flare temperature observed during tissue hyperemia, may be as high as 12 deg F. 11. Males on the average have larger flare patterns than females, 5.7 in.2 and 4.7 in.2, respectively. The flare areas were computed from thermograms taken 2 to 3 minutes after off-loading of tissue. 12. With the average distance from the buttock's fold to the highest and lowest thermal flare indication being lower for females (3.2 and 5.9) than for males (3.8 and 6.4), a relationship between the site or decubitus ulcer formation and the pelvic bone structure of the sexes may well exist. 13. No two thermal flare patterns are similar either in size or in shape. Thermal flare patterns occur along the centerline of the body at the sacrum and coccyx level. 14...

Adolescent

From egg to pole cells: ultrastructural aspects of early cleavage and germ cell determination in insects.

Insect eggs are giant and very complex cells covered by an extremely resistant shell. Both the egg cell and surrounding eggshell express anteroposterior and ventrodorsal polarity. The molecular and cytoplasmic organization of both axes originates during oogenesis and leads to the production of an ooplasmic system which consists of euplasm and deutoplasm (yolk) and contains a nucleus as well as extranuclear determinants of maternal origin. Both are part of the store of information for early embryogenesis. In addition, the deutoplasm serves as raw material and early nutrient supply for building the embryo. The insect egg cell, which is arrested in the first maturation division when released from the ovary during oviposition, will be activated by different stimuli among different species to complete meiosis and start embryogenesis. The zygote nucleus undergoes a number of synchronous mitotic divisions leading to cleavage energids which initially form a syncytial blastoderm and subsequently the cellular blastoderm. In many insects, prior to blastoderm formation, polar granules (or oosome material) are incorporated in a single cell or a small number of cells which bud off at the posterior pole. These so called pole cells give rise to the primordial germ cells. Therefore, polar granules or the oosome material mark the germ line, and while structural counterparts of determinants of body pattern formation have so far not been found, the polar granules or oosome serve as an autonomous ooplasmic determinant for the pole or germ cells. Anteroposterior body polarity can arise independent of the germ plasm.

Animals

Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos.

The Krüppel (Kr) locus is a member of the 'gap' class of segmentation genes of Drosophila melanogaster. Mutations at the Kr locus cause the deletion of contiguous segments from the embryonic body pattern. We have elucidated the spatial and temporal characteristics of Kr gene expression during early embryo development, the localization of cytoplasmic Kr+ activity and its spatial requirement for normal segmentation.

Animals

A gene involved in the development of the posterior body region of C. elegans.

Many regional differences in Caenorhabditis elegans body pattern are generated after hatching. Here I describe a gene, mab-5, that is required for the postembryonic development of nearly all ectodermal and mesodermal features that normally characterize a posterior body region. In addition, this gene is necessary for most cell migrations toward the posterior, but not for cell migrations toward the anterior. mab-5+ activity is cell-autonomous. In animals carrying a mutation in the gene lin-22, increases or decreases in mab-5+ gene dosage produce corresponding increases or decreases in the size of the region in which cells adopt posterior-specific fates. The model that best explains the data is that during postembryonic development, posterior-specific patterns of cell differentiation and cell migration are initiated by graded positional information, and that a common step in the different cellular responses to this information is mediated by mab-5 activity.

Animals

Regressive language in severe head injury.

In a follow-up study of 50 patients with severe head injuries three patients had echolalia. One patient with initially global aphasia had echolalia for some weeks when he started talking. Another patient with severe diffuse brain damage, dementia, and emotional regression had echolalia. The dysfunction was considered a detour performance. In the third patient echolalia and palilalia were details in a total pattern of regression lasting for months. The patient, who had extensive frontal atrophy secondary to a very severe head trauma, presented an extreme state of regression returning to a foetal-body pattern and behaving like a baby.

Adolescent

The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.

A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains. This paper deals with one of these genes, Xlim-1. Xlim-1 mRNA is found at low abundance in the unfertilized egg, has a major expression phase at the gastrula stage, decreases, and rises again during the tadpole stage. In adult tissues the brain shows the highest abundance, by far, of Xlim-1 mRNA. The maternal and late expression phases of the Xlim-1 gene suggest that it has multiple functions at different stages of the Xenopus life cycle. In the gastrula embryo, Xlim-1 mRNA is localized in the dorsal lip and the dorsal mesoderm, that is, in the region of Spemann's organizer. Explant experiments showed that Xlim-1 mRNA is induced by the mesoderm-inducer activin A and by retinoic acid, which is not a mesoderm inducer but affects patterning during Xenopus embryogenesis; application of activin A and retinoic acid together results in synergistic induction. The structure, inducibility, and localized expression in the organizer of the Xlim-1 gene suggest that it has a role in establishing body pattern during gastrulation.

Activins

Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo.

The metameric organisation of the Drosophila embryo is generated early during development, due to the action of maternal effect and zygotic segmentation and homeotic genes. The gap genes participate in the complex process of pattern formation by providing a link between the maternal and the zygotic gene activities. Under the influence of maternal gene products they become expressed in distinct domains along the anteroposterior axis of the embryo; negative interactions between neighboring gap genes are thought to be involved in establishing the expression domains. The gap gene activities in turn are required for the correct patterning of the pair-rule genes; little is known, however, about the underlying mechanisms. We have monitored the distribution of gap and pair-rule genes in wild-type embryos and in embryos in which the anteroposterior body pattern is greatly simplified due to combinations of maternal effect mutations (staufen exuperantia, vasa exuperantia, vasa exuperantia, bicoid oskar, bicoid oskar torsolike, vasa torso exuperantia). We show that the domains of protein distribution of the gap genes hunchback and Krüppel overlap in wild-type embryos. Based on the analysis of the maternal mutant combinations, we suggest an explanation of how this overlap is generated. Furthermore, our data show that different constellations of gap gene activities provide different input for the pair-rule genes, and thus strongly suggest that the overlap of hunchback and Krüppel in wild-type is functional in the formation of the patterns of pair-rule genes.

Animals

Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo.

Segmental pattern formation in Drosophila proceeds in a hierarchical manner whereby the embryo is stepwise divided into progressively finer regions until it reaches its final metameric form. Maternal genes initiate this process by imparting on the egg a distinct antero-posterior polarity and by directing from the two polar centres the activities of the zygotic genes. The anterior system is strictly dependent on the product of the maternal gene bicoid (bcd), without which all pattern elements in the anterior region of the embryo fail to develop. The posterior system seems to lack such a morphogen. Rather, the known posterior maternal determinants simply define the boundaries within which abdominal segmentation can occur, and the process that actively generates the abdominal body pattern may be entirely due to the interactions between the zygotic genes. The most likely candidates among the zygotic genes that could fulfil the role of initiating the posterior pattern-forming process are the gap genes, as they are the first segmentation genes to be expressed in the embryo. Here we describe the interactions between the gap genes Krüppel (Kr), knirps (kni) and tailless (tll). We show that kni expression is repressed by tll activity, whereas it is directly enhanced by Kr activity. Thus, Kr activity is present throughout the domain of kni expression and forms a long-range protein gradient, which in combination with kni activity is required for abdominal segmentation of the embryo.

Animals

cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos.

The dorsoventral pattern of the Drosophila embryo is mediated by a gradient of nuclear localization of the dorsal protein which acts as a morphogen. Establishment of the nuclear concentration gradient of dorsal protein requires the activities of the 10 maternal 'dorsal group' genes whose function results in the positive regulation of the nuclear uptake of the dorsal protein. Here we show that in contrast to the dorsal group genes, the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein. While loss of function mutations of any of the dorsal group genes lead to dorsalized embryos, loss of cactus function results in a ventralization of the body pattern. Progressive loss of maternal cactus activity causes progressive loss of dorsal pattern elements accompanied by the expansion of ventrolateral and ventral anlagen. However, embryos still retain dorsoventral polarity, even if derived from germline clones using the strongest available, zygotic lethal cactus alleles. In contrast to the loss-of-function alleles, gain-of-function alleles of cactus cause a dorsalization of the embryonic pattern. Genetic studies indicate that they are not overproducers of normal activity, but rather synthesize products with altered function. Epistatic relationships of cactus with dorsal group genes were investigated by double mutant analysis. The dorsalized phenotype of the dorsal mutation is unchanged upon loss of cactus activity. This result implies that cactus acts via dorsal and has no independent morphogen function. In all other dorsal group mutant backgrounds, reduction of cactus function leads to embryos that express ventrolateral pattern elements and have increased nuclear uptake of the dorsal protein at all positions along the dorsoventral axis. Thus, the cactus gene product can prevent nuclear transport of dorsal protein in the absence of function of the dorsal group genes. Genetic and cytoplasmic transplantation studies suggest that the cactus product is evenly distributed along the dorsoventral axis. Thus the inhibitory function that cactus product exerts on the nuclear transport of the dorsal protein appears to be antagonized on the ventral side. We discuss models of how the action of the dorsal group genes might counteract the cactus function ventrally.

Alleles

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

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