Developmental genetics

Summary Of particular concern to the human geneticist are the effects of genetic abnormalities on development. To gain an understanding of these effects it is necessary to engage in a reciprocal process of using knowledge of normal developmental events to elucidate the mechanisms operative in abnormal situations and then of using what is learned about these abnormal situations to expand our understanding of the normal. True developmental genes have not been described in man, although it is likely that they exist, but many developmental abnormalities are ascribable to mutations in genes coding for enzymes and structural proteins. Some of these even produce multiple malformation syndromes with dysmorphic features. These situations provide a precedent for asserting that not only monogenic developmental abnormalities, but also abnormalities resulting from chromosome imbalance must ultimately be explicable in molecular terms. However, the major problem confronted by the investigator interested in the pathogenesis of any of the chromosome anomaly syndromes is to understand how the presence of an extra set of normal genes or the loss of one of two sets of genes has an adverse effect on development. Several molecular mechanisms for which limited precedents exist may be considered on theoretical grounds. Because of the difficulties in studying developmental disorders in man, a variety of experimental systems have been employed. Particularly useful has been the mouse, which provides models for both monogenic and aneuploidy produced abnormalities of development. An example of the former is the mutation oligosyndactylism which in the heterozygous state causes oligosyndactyly and in the homozygous state causes early embryonic mitotic arrest. All whole arm trisomies and monosomies of the mouse can be produced experimentally, and of special interest is mouse trisomy 16 which has been developed as an animal model of human trisomy 21 (Down syndrome). In the long run, the most direct approach to elucidating the genetic problems of human development will involve not only the study of man himself but also of the appropriate experimental models in other species.Acknowledgments. This review was written while the author was a Henry J. Kaiser Senior Fellow at the Center for Advanced Study in the Behavioral Sciences, Palo Alto, California. This work was supported by grants from the National Institutes of Health (GM-24309, HD-03132, HD-15583, HD-17001) and the American Cancer Society (CD-119) and by a contract from the National Institute of Child Health and Human Development (NOI-HD-2858).     

Developmental genetics

Of particular concern to the human geneticist are the effects of genetic abnormalities on development. To gain an understanding of these effects it is necessary to engage in a reciprocal process of using knowledge of normal developmental events to elucidate the mechanisms operative in abnormal situations and then of using what is learned about these abnormal situations to expand our understanding of the normal. True developmental genes have not been described in man, although it is likely that they exist, but many developmental abnormalities are ascribable to mutations in genes coding for enzymes and structural proteins. Some of these even produce multiple malformation syndromes with dysmorphic features. These situations provide a precedent for asserting that not only monogenic developmental abnormalities, but also abnormalities resulting from chromosome imbalance must ultimately be explicable in molecular terms. However, the major problem confronted by the investigator interested in the pathogenesis of any of the chromosome anomaly syndromes is to understand how the presence of an extra set of normal genes or the loss of one of two sets of genes has an adverse effect on development. Several molecular mechanisms for which limited precedents exist may be considered on theoretical grounds. Because of the difficulties in studying developmental disorders in man, a variety of experimental systems have been employed. Particularly useful has been the mouse, which provides models for both monogenic and aneuploidy produced abnormalities of development. An example of the former is the mutation oligosyndactylism which in the heterozygous state causes oligosyndactyly and in the homozygous state causes early embryonic mitotic arrest. All whole arm trisomies and monosomies of the mouse can be produced experimentally, and of special interest is mouse trisomy 16 which has been developed as an animal model of human trisomy 21 (Down syndrome). In the long run, the most direct approach to elucidating the genetic problems of human development will involve not only the study of man himself but also of the appropriate experimental models in other species.     

Developmental studies inDrosophila. IV. Quantitative protein changes in organs and whole-fly homogenates during development ofD. pseudoobscura

Résumé Les protéines présentes à différents moments de l'ontogenèse dans les glandes salivaires, l'hémolymphe, le corps adipeux, la paroi du corps et les individus entiers deDrosophila pseudoobscura ont été analysées grâce à une technique nouvelle de micro-électrophorèse discale.

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Supported in part by grants No. GM-16736 and No. FR-05426 from the Department of Health, Education, and Welfare. We thank Dr.R. Putman for allowing us to use some of his equipment.     

Developmental G6PD polymorphism in Drosophila melanogaster: evidence for non-structural variants.

G6PD isozyme variation in Drosophila melanogaster is investigated in the larval stage through electrophoretic and genetic analyses. As current structural models for this gene-enzyme system fail to apply in these laboratory populations, the authors suggest a regulatory hypothesis to explain their observations.     

Developmental change of EEG in rat from 4th to 16th week.

The development of EEG in 8 male rats from 4 to 16 weeks age were studied chronically. Theta band had the highest power at 5--16 weeks. Especially after 11 weeks, theta band presented a significantly higher peak than that of 4-week-old. In contrast to this, delta band, which had the highest power at 4 weeks, was markedly decreased.     

Nerve endings isolated from chick embryonic optic tectum. 2. Developmental aspects of synaptosomal membrane

Summary Fractions enriched in nerve endings (synaptosomes) have been isolated from chick embryonic optic tectum during development. After osmotic shock, these fractions appeared to be enriched in membranes which during development acquire typical features of mature synaptosomal membranes.     

Nerve endings isolated from chick embryonic optic tectum. 1. Developmental aspects of intact synaptosomes

Summary Fractions enriched in nerve endings (synaptosomes) have been isolated from optic tectum of chick embryos at 16 and 18 days of incubation and of chicks immediately after hatching. Morphological aspects of nerve endings have been examined with special regard to the appearance of synaptic thickenings and synaptic vesicles.     

Developmental and pathological angiogenesis in the central nervous system

Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases.     

Developmental patterns of supercooling capacity in a subantarctic wingless fly

Anatalanta aptera is a wingless fly which lives in subantarctic islands, particularly in sea bird colonies. Developmental patterns of supercooling capacity were studied in an experimental population reared at 5°C and fed ad libitum. Mean supercooling points of the eggs, second and third instar larvae, pupae, teneral and mature adults were –28.0°C, –10.8°C, –8.8°C, 17.6°C, –16.6°C and –8.2°C respectively. Low mean supercooling points were found for inactive stages (eggs, pupae) and, unexpectedly among Diptera, teneral adults. Mature adults had a combination of low supercooling ability, high lipid content and physogastry. The results are compared with those obtained in winged species from other families of Diptera.     

Developmental actions of natriuretic peptides in the brain and skeleton

The concept that atrial natriuretic peptide (ANP) and the closely related peptides BNP and CNP might be involved in the ontogeny of several organ systems emerged in the late 1980s. While many of the reported in vitro actions have not been examined in the context of organ development in vivo, recent studies demonstrate that mice which lack or overexpress natriuretic peptides or receptors exhibit pronounced skeletal growth defects. This article discusses how natriuretic peptides and other factors appear to regulate bone growth as an example of how natriuretic peptides might participate in the ontogeny of other organ systems. Evidence indicating that natriuretic peptides regulate neural development is then reviewed. Natriuretic peptides and receptors exhibit complex expression patterns in the developing nervous system, where they have been shown to act on neural cells as early as at the embryonic neural tube stage. Interestingly, both bone and brain growth appear to utilize primarily CNP and the CNP-specific type B receptor, and perhaps the type C receptor. In vitro data indicate that CNP may act on developing neurons, astrocytes and Schwann cells like a classical growth factor, regulating proliferation, patterning, phenotypic specification, survival and axonal pathfinding. Natriuretic peptides might also have roles in the vascularization of the embryonic brain, establishment of the blood-brain and blood-nerve barriers, and perhaps in nerve regeneration.Received 13 April 2004; received after revision 20 May 2004; accepted 27 May 2004     

Developmental forms of human skeletal muscle AMP-deaminase

Chromatography on phosphocellulose revealed the existence of two well-separable forms of skeletal muscle AMP-deaminase in the tissue extracts of 11- and 16-week-old human fetuses. One of these forms elutes from the column at the same salt concentration as the muscle isozyme found in the skeletal muscle extract from adult man, and seems to have similar kinetic properties. The second form, which was found only in vestigial amounts in adult human tissue extract, represents different kinetic properties and seems to be a form characteristic for the fetal period of ontogenesis.     

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral, neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission, and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845) GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes.