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PubMedDate not supplied

The Evolution of Developmental Mechanisms. Proceedings of a symposium. London, United Kingdom, January 2001.

In 1829, von Baer proposed four principles of development, the first of which states that the embryos of a large group of animals have most in common at early stages of development, the specialised features of different subgroups only emerging later. After the publication of Darwin's The Origin of Species in 1859, the relevance of von Baer's principles to evolution was clear to many biologists, who assessed evolutionary relationships on the basis of similarities and differences between early embryos. The validity of these comparisons, carried out more than a century ago, has been confirmed by recent molecular analyses. These new gene-based comparisons have in turn led to a renewed interest in the scientific literature of the first half of the 20th century, which documented in great detail comparative anatomical studies of living and fossil animals. The past decade has seen a growing synergy between developmental biology and evolutionary studies. As a result, not only is an evolutionary perspective now integral to developmental studies, but palaeontologists have become deeply interested in embryos. This integration was the subject of the symposium of the Winter Meeting of the Anatomical Society, held in London in January 2001, entitled 'The Evolution of Developmental Mechanisms'. It was a very stimulating and enjoyable meeting that addressed the theme at a number of levels, ranging from the major evolutionary changes resulting from gene duplication to the fine detail of insect wing vein evolution. These two ends of the spectrum of topics reflect Darwin's perspective on von Baer's principles, i.e. his recognition that homologies between different phyla are to be seen in early embryonic and larval structures, while adaptations that enable an organism to survive in its particular environment are the result of changes acting late in development. The reviews brought together in this volume represent a thoughtful and thought-provoking synthesis of data collected over many years. They show the rewards of detailed and long-term study of embryos that in some cases are difficult to obtain, but represent living clues to the mechanisms underlying important evolutionary transitions. We feel privileged to have had the responsibility for editing this impressive issue of the Journal of Anatomy, which will, we have no doubt, be a significant landmark in the ongoing story of development and evolution, and will be widely cited.

Animals↗
PubMed1991

The complete primary structure of type XII collagen shows a chimeric molecule with reiterated fibronectin type III motifs, von Willebrand factor A motifs, a domain homologous to a noncollagenous region of type IX collagen, and short collagenous domains with an Arg-Gly-Asp site.

Extracellular matrix molecules are generally categorized as collagens, elastin, proteoglycans, or other noncollagenous structural/cell interaction proteins. Many of these extracellular proteins contain distinctive repetitive modules, which can sometimes be found in other proteins. We describe the complete primary structure of an alpha 1 chain of type XII collagen from chick embryonic fibroblasts. This large, structurally chimeric molecule identified by cDNA analysis combines previously unrelated molecular domains into a single large protein 3,124 residues long (approximately 340 kD). The deduced chicken type XII collagen sequence starts at the amino terminus with one unit of the type III motif of fibronectin, which is followed by one unit homologous to the von Willebrand factor A domain, then one more fibronectin type III module, a second A domain from von Willebrand factor, 6 units of type III motif and a third A domain, 10 consecutive units of type III motif and a fourth A domain, a domain homologous to the NC4 domain peptide of type IX collagen, and finally two short collagenous regions previously described as part of the partially sequenced collagen type XII molecule; an Arg-Gly-Asp potential cell adhesive recognition sequence is present in a hydrophilic region at the terminus of one collagenous domain. Antibodies raised to type XII collagen synthesized in a bacterial expression system recognized not only previously reported bands (220 kD et cetera) in tendons, but also bands with apparently different molecular sizes in fibroblasts and 4-d embryos. The antibodies stained a wide variety of extracellular matrices in embryos in patterns distinct from those of fibronectin or interstitial collagens. They prominently stained extracellular matrix associated with certain neuronal tissues, such as axons from dorsal root ganglia and neural tube. These studies identify a novel chimeric type of molecule that contains both adhesion molecule and collagen motifs in one protein. Its structure blurs current classification schemes for extracellular proteins and underscores the potentially large diversity possible in these molecules.

Amino Acid Sequence↗
PubMed2004

Cranial neural crest recycle surface integrins in a substratum-dependent manner to promote rapid motility.

Cell migration is essential for proper development of numerous structures derived from embryonic neural crest cells (NCCs). Although the migratory pathways of NCCs have been determined, the molecular mechanisms regulating NCC motility remain unclear. NCC migration is integrin dependent, and recent work has shown that surface expression levels of particular integrin alpha subunits are important determinants of NCC motility in vitro. Here, we provide evidence that rapid cranial NCC motility on laminin requires integrin recycling. NCCs showed both ligand- and receptor-specific integrin regulation in vitro. On laminin, NCCs accumulated internalized laminin but not fibronectin receptors over 20 min, whereas on fibronectin neither type of receptor accumulated internally beyond 2 min. Internalized laminin receptors colocalized with receptor recycling vesicles and were subsequently recycled back to the cell surface. Blocking receptor recycling with bafilomycin A inhibited NCC motility on laminin, indicating that substratum-dependent integrin recycling is essential for rapid cranial neural crest migration.

Animals↗
PubMed2004

Role of heparan sulfate in dextral heart looping in chick.

Heparan sulfate (HS) has been shown to be involved in left-right asymmetry formation, including the process of dextral heart looping during embryonic development. The structural features of HS required in this process, however, have not been explored. In this study, we examined the structure of HS from the heart-forming regions (or heart fields) of Hamburger and Hamilton stage 5-9 chick embryos. No significant differences were found in HS to chondroitin sulfate (CS) ratio, HS chain length, or [35S] sulfate incorporation at HS disaccharide level between the left and the right heart fields. Compared to other parts of the embryo, however, lower ratio of HS to CS, shorter HS chain length, and higher [35S] sulfate incorporation at 6-O position of the glucosamine residue in the HS chains were observed in the heart-forming regions. Moreover, HS from the left and the right heart fields exhibit differential cleavage by heparanase, an endo-beta-d- glucuronidase that cleaves specific sequences within the HS chain. In embryo culture, microinjection of the active human heparanase enzyme into the right but not the left pericardial cavity at stage 7-8+ resulted in reversed heart looping in a dose-dependent manner. Heart reversal following microinjection of heparin or heparin derivatives suggests the involvement of N- and 6-O-sulfation but not 2-O-sulfation in the heart looping process.

Animals↗
PubMed1984

Tissue disposition of carbon disulfide. II. Whole-body autoradiography of 35S- and 14C-labelled carbon disulfide in pregnant mice.

Occupational exposure to carbon disulfide (CS2) has been associated with an increased rate of spontaneous abortions. Animal experiments have shown that CS2 is embryotoxic and teratogenic. In the present study, the embryonal and foetal distribution of CS2 and its metabolites was studied after administration of 35S- or 14C-labelled CS2 to pregnant mice in different stages of gestation. CS2 and its metabolites passed the placenta at all stages of gestation. High levels of metabolites of CS2 were registered in the embryonic neuroepithelium. In mid and late gestation CS2 itself accumulated in the cerebrospinal fluid (CSF) of the brain. 14C-labelled metabolites of CS2 showed affinity for bone and were retained in the liver even at long survival times (24 hours). These localizations may be of significance for some of the reported teratogenic effects of CS2, such as hydrocephalus, ossification defects and foetal liver injury, and support the idea that CS2 and/or its metabolites are embryotoxic and teratogenic by acting directly on embryonal and foetal structures.

Animals↗
PubMed1978

Nucleotide sequence relationship between intracisternal type A particles of Mus musculus and an endogenous retrovirus (M432) of Mus cervicolor.

Intracisternal type A particles are retrovirus-like structures found in embryonic cells and many tumors of Mus musculus but having no clear relationship with other retroviruses of this mouse species. We have observed a partial nucleotide sequence homology between the high-molecular-weight (32S and 35S) RNA components of intracisternal A-particles from a neuroblastoma cell line and the 70S RNA fraction from M432, a type of retrovirus endogenous to the Asian mouse Mus cervicolor. M432 complementary DNA (cDNA) was hybridized to the extent of 30% by the A-particle RNAs. The hybrids showed a lower thermal stability (DeltaT(m), 7 degrees C) than those formed with homologous RNA. The reaction was commensurate with that found between M432 cDNA and divergent sequences in the M. musculus genome. The capacity to hybridize M432 cDNA was closely correlated with the concentration of A-particle sequences in the cytoplasmic RNA of several M. musculus cell types. The major RNA fraction of M432 virus showed a reciprocal partial reaction with the A-particle cDNA's; the virus, which was grown in NIH/3T3 (M. musculus) cells, also contained a small proportion of apparently authentic A-particle nucleotide sequences. A subset of A-particle sequences seemed to be almost totally lacking in the main M432 RNA. The A-particle cDNA's hybridized extensively with divergent sequences in M. cervicolor cellular DNA, indicating that this mouse species may contain not only the partially homologous M432 virogene, but also a more complete genetic equivalent of the intracisternal A-particle.

Animals↗
PubMed1992

Sonography of occult dysraphism in neonates and infants with MR imaging correlation.

High-resolution spinal sonography has become an accepted study to screen for occult dysraphic lesions (ODLs) in neonates and infants. These defects are thought to be caused by abnormal fusion or closure of embryonic dorsal midline structures. Sonographic findings suggestive of an ODL include low position of the conus, nontapered bulbous appearance of the conus, dorsal location of the cord within the bony canal, solid or cystic masses in the distal canal or soft tissue of the back extending toward the canal, patulous distal thecal sac, and thick filum. Physical findings suggestive of ODLs include lumbosacral skin dimples, lumbosacral masses, lower extremity weakness, and an extra appendage arising from the back. The appearances of a normal infant spine, dorsal dermal sinus, lipoma, lipomyelomeningocele, lipomyelocele, myelocystocele, and diastematomyelia are depicted sonographically and correlate with those on magnetic resonance (MR) images. MR imaging is most useful when sonographic findings are abnormal or equivocal or when normal skeletal maturation limits sonographic visualization of the intracanalicular contents.

Cauda Equina↗
PubMed2006

Quantifying cardiovascular flow dynamics during early development.

The relationship between developing biologic tissues and their dynamic fluid environments is intimate and complex. Increasing evidence supports the notion that these embryonic flow-structure interactions influence whether development will proceed normally or become pathogenic. Genetic, pharmacological, or surgical manipulations that alter the flow environment can thus profoundly influence morphologic and functional cardiovascular phenotypes. Functionally deficient phenotypes are particularly poorly described as there are few imaging tools with sufficient spatial and temporal resolution to quantify most intra-vital flows. The ability to visualize biofluids flow in vivo would be of great utility in functionally phenotyping model animal systems and for the elucidation of the mechanisms that underlie flow-related mechano-sensation and transduction in living organisms. This review summarizes the major methodological advances that have evolved for the quantitative characterization of intra-vital fluid dynamics with an emphasis on assessing cardiovascular flows in vertebrate model organisms.

Animals↗
PubMed1994

Immunocytochemical localization of cytochromes P450 17 alpha-hydroxylase and aromatase in embryonic cell layers of elongating porcine blastocysts.

Localized expression of cytochromes P450 17 alpha-hydroxylase (P450c17) and aromatase (P450arom) was investigated in embryonic cell layers of elongating porcine blastocysts by immunocytochemistry. Blastocysts were flushed from the uterus on day 12 of pregnancy, fixed in paraformaldehyde, embedded in paraffin, sectioned, and stained using immunogold- and peroxidase-based techniques. Staining for both P450c17 and P450arom was intense in spherical 7- to 10-mm blastocysts, but was absent in earlier stage 2- to 4-mm blastocysts and less intense or absent in later stage 20-mm and filamentous embryos. Cytochrome P450c17 was limited to the trophoblast of all blastocysts expressing the enzyme, and in spherical 7- to 10-mm blastocysts, essentially all cells of the trophoblast layer stained positively for P450c17. However, as elongation became apparent in 10-mm blastocysts, the cells of the trophoblast became flattened, and the expression of P450c17 declined particularly in those trophoblast cells adjacent to the embryonic disc where mesoderm outgrowth was occurring. In fact, two distinct populations of trophoblast cells became obvious: one that maintained P450c17 expression, and one that did not. Moreover, those trophoblast cells expressing P450c17 were less flattened than neighboring cells in which P450c17 expression was absent. These two morphologically and functionally distinct trophoblastic cell populations were most obvious in areas furthest from the embryonic disc. Cytochrome P450arom was expressed in the trophoblast as well as the hypoblast under the embryonic disc. Neither P450c17 nor P450arom appeared to be expressed in the embryonic disc or the mesoderm of the expanding blastocyst. These functional and structural changes in the embryonic cell layers of the elongating conceptus may be associated with the transient synthesis and secretion of estrogen that occur at the time of maternal recognition of pregnancy in the pig.

Animals↗
PubMed1994

Immunocytochemical localization of cytochromes P450 17 alpha-hydroxylase and aromatase in embryonic cell layers of elongating porcine blastocysts.

Localized expression of cytochromes P450 17 alpha-hydroxylase (P450c17) and aromatase (P450arom) was investigated in embryonic cell layers of elongating porcine blastocysts by immunocytochemistry. Blastocysts were flushed from the uterus on day 12 of pregnancy, fixed in paraformaldehyde, embedded in paraffin, sectioned, and stained using immunogold- and peroxidase-based techniques. Staining for both P450c17 and P450arom was intense in spherical 7- to 10-mm blastocysts, but was absent in earlier stage 2- to 4-mm blastocysts and less intense or absent in later stage 20-mm and filamentous embryos. Cytochrome P450c17 was limited to the trophoblast of all blastocysts expressing the enzyme, and in spherical 7- to 10-mm blastocysts, essentially all cells of the trophoblast layer stained positively for P450c17. However, as elongation became apparent in 10-mm blastocysts, the cells of the trophoblast became flattened, and the expression of P450c17 declined particularly in those trophoblast cells adjacent to the embryonic disc where mesoderm outgrowth was occurring. In fact, two distinct populations of trophoblast cells became obvious: one that maintained P450c17 expression, and one that did not. Moreover, those trophoblast cells expressing P450c17 were less flattened than neighboring cells in which P450c17 expression was absent. These two morphologically and functionally distinct trophoblastic cell populations were most obvious in areas furthest from the embryonic disc. Cytochrome P450arom was expressed in the trophoblast as well as the hypoblast under the embryonic disc. Neither P450c17 nor P450arom appeared to be expressed in the embryonic disc or the mesoderm of the expanding blastocyst. These functional and structural changes in the embryonic cell layers of the elongating conceptus may be associated with the transient synthesis and secretion of estrogen that occur at the time of maternal recognition of pregnancy in the pig.

Animals↗
PubMed1991

Expression in non-lens tissues of an enzyme activity related to the 'lens-specific' protein, delta crystallin.

When chick embryo neutral retina (NR) cells are cultured for long periods in vitro, they undergo extensive transdifferentiation into lens and express the lens protein, delta crystallin. We now demonstrate that this process is accompanied by a change in the chromatin conformation of the delta-gene locus from DNAase1-resistant to DNAase1-sensitive in the nuclei of most cells. Transcripts hybridising to a delta probe are also much more prevalent among the in vitro transcription products from lens or transdifferentiated NR culture nuclei, as compared to nuclei from fresh NR tissue. Published evidence indicates that the chick delta 1 crystallin gene encodes the major structural protein of embryonic lens fibres, whereas the closely related delta 2 gene may encode the urea-cycle enzyme argininosuccinate lyase (ASL). Our present data lends further support to this view. Both immunodetectable delta-related protein(s) and ASL activity are present in fresh embryonic NR tissue, as well as in mouse and Rana liver, and in Rana lens. Our polyclonal anti-delta antibody also cross-reacts with a major constituent of commercial bovine ASL, of the same molecular size as chick delta crystallin. Immunoselection studies suggest that the ASL activity in chick embryonic NR is conferred mainly by the delta-related protein band. So-called 'ectopic' expression of delta crystallin in embryonic NR (and other tissues) may thus involve the delta 2/ASL gene, and could reflect some metabolic requirement for ASL activity.

Animals↗
PubMed1995

Analysis of the genetic hierarchy guiding wing vein development in Drosophila.

The Drosophila rhomboid (rho) and Egf-r genes are members of a small group of genes required for the differentiation of various specific embryonic and adult structures. During larval and early pupal development expression of rho in longitudinal vein primordia mediates the localized formation of wing veins. In this paper we investigate the genetic hierarchy guiding vein development, by testing for genetic interactions between rho alleles and a wide variety of wing vein mutations and by examining the pattern of rho expression in mutant developing wing primordia. We identify a small group of wing vein mutants that interact strongly with rho. Examination of rho expression in these and other key vein mutants reveals when vein development first becomes abnormal. Based on these data and on previous genetic analyses of vein formation we present a sequential model for establishment and differentiation of wing veins.

Animals↗
PubMed1995

The role of Hoxa-3 in mouse thymus and thyroid development.

Targeted disruption of Hoxa-3 results in a number of regionally restricted defects in tissues and structures derived from or patterned by mesenchymal neural crest. However, analysis of mutant embryos with injections of a carbocyanine dye or with molecular markers that label these cells indicates that neither the amount nor the migration patterns of this neural crest population are grossly affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic capacity of this neural crest cell population to differentiate and/or to induce proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa-3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is first evident as an expansion of mesenchymal neural crest in the posterior part of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1 expression is observed in these cells in the mutant embryos. As pax-1 mutant mice also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to maintain pax-1 expression in these cells and that the reduction of pax-1 expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid gland is formed from the fusion of two structures of separate embryonic origin, the thyroid diverticulum, which is formed from endodermal epithelium in the floor of the pharynx, and the ultimobranchial body, formed from mesenchymal neural crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are defective in mutant mice. Often a vesicle is observed in mutant mice that is exclusively composed of calcitonin-producing cells, suggesting the persistence of an ultimobranchial body. Both aspects of the thyroid phenotype show variable expressivity among mutant animals, even on the two sides of the same mutant animal. This variability suggests the presence of a compensating gene or genes, whose utilization is stochastic. A reasonable candidate for providing this compensatory function is the paralogous gene Hoxb-3.

Animals↗
PubMed1998

Reciprocal temporospatial patterns of Msx2 and Osteocalcin gene expression during murine odontogenesis.

Msx2 is a homeodomain transcription factor that regulates craniofacial development in vivo and osteocalcin (Osc) promoter activity in vitro. Msx2 is expressed in many craniofacial structures prior to embryonic day (E) E14 but is expressed at later stages in a restricted pattern, primarily in developing teeth and the calvarium. We examine Osc expression by in situ hybridization during murine development, detailing temporospatial relationships with Msx2 expression during preappositional and appositional odontogenesis and calvarial osteogenesis. Osc expression at E14-14.5 is very low, limited to a few perichondrial osteoblasts in the dorsal aspect of developing ribs. At E16.5 and E18.5, Osc expression is much higher, widely expressed in skeletal osteoblasts, including calvarial osteoblasts that do not express Msx2. No Osc is detected in early preappositional teeth that express Msx2. In incisors studied at an early appositional phase, Msx2 is widely expressed in the tooth, primarily in ovoid preodontoblasts and subjacent dental papilla cells. Osc is detected only in a small number of maturing odontoblasts that also express alpha1(I) collagen (Colla1) and that are postproliferative (do not express histone H4). Msx2 expression greatly overlaps both histone H4 and Colla1 expression in ovoid preodontoblasts and dental papilla cells. By the late appositional phases of E18.5 and neonatal teeth, Osc mRNA is highly expressed in mature columnar odontoblasts adjacent to accumulating dentin. In appositional bell-stage molars, reciprocal patterns of Msx2 and Osc are observed in adjacent preodontoblasts and odontoblasts within the same tooth. Osc is expressed in mature columnar odontoblasts, while Msx2 is expressed in adjacent immature ovoid preodontoblasts. In less mature teeth populated only by immature ovoid preodontoblasts, only Msx2 is expressed-no Osc is detected. Thus, Msx2 and Osc are expressed in reciprocal patterns during craniofacial development in vivo, and Msx2 expression in preodontoblasts clearly precedes Osc expression in odontoblasts. In functional studies using MC3T3-E1 calvarial osteoblasts, Msx2 suppresses endogenous Osc, but not osteopontin, mRNA accumulation. In toto, these data suggest that Msr2 suppresses Osc expression in the craniofacial skeleton at stages immediately preceding odontoblast and osteoblast terminal differentiation.

Animals↗
PubMed1999

Heparan sulfate and cell division.

Heparan sulfate is a component of vertebrate and invertebrate tissues which appears during the cytodifferentiation stage of embryonic development. Its structure varies according to the tissue and species of origin and is modified during neoplastic transformation. Several lines of experimental evidence suggest that heparan sulfate plays a role in cellular recognition, cellular adhesion and growth control. Heparan sulfate can participate in the process of cell division in two distinct ways, either as a positive or negative modulator of cellular proliferation, or as a response to a mitogenic stimulus.

Animals↗
PubMed2001

Neurodevelopmental risk factors in schizophrenia.

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.

Brain Diseases↗
PubMed1983

Factors in manifestation of developmental abnormalities of the central nervous system by environmental agents.

The developing brain can be regarded as one the embryonic and fetal structures most susceptible to teratogenic insults, because of its longlasting sensitive period, a great vulnerability of the undifferentiated neural cells and no further reproductive capacity of neurons. Among the factors in manifestation of brain malformations, developmental stage-dependent susceptibility to teratogens and sensitive period for teratogenesis are the most important one which characterize developmental toxicity. The mammalian proliferating matrix cells in the developing brain are particularly sensitive to teratogenic insults at the time when the matrix cells start to differentiate into cortical neuron. As the factors determining the vulnerability of matrix cells, proliferative and metabolic state, restoration capacity and phase of chemical differentiation prior to actual differentiation were discussed.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

[The first appearance of Meckel's cartilage in the fetus].

Meckel's cartilage plays an important role in the topographical organisation and in the differentiation of the facial structure during the embryonal and even much later during the foetal period. Our observations on serial sections carried out in two human foetuses aged 12 and 16 weeks indicate that the two dorsal (tympanic) and ventral (mandibular) branches of Meckel's cartilage are perfectly defined at 16 weeks. In the dorsal branch, the primordia of the incus and of head of the malleus are still composed on non-ossified cartilage. In the ventral branch, it is also possible to describe at 16 weeks three posterior, medial and anterior parts which are composed of cartilage. The initiating role played by the ventral part of Meckel's cartilage on the ossification of the mandible leads during the embryonal period to the formation of the mandibular primary growth center, which is therefore clearly defined in our first stage at 12 weeks. The partial fibrous evolution and the regression of the major part of the ventral branch of Meckel's cartilage only start after 16 weeks of intrauterine life.

Branchial Region↗