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PubMed1982

Effects of phorbol ester tumor promoters and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells.

The effect of phorbol ester tumor promoters on neurite outgrowth was studied in cultured human neuroblastoma cell lines and in cultured embryonic chick and neonatal rat sympathetic ganglia. Promoters inhibited nerve growth factor (NGF)-stimulated neurite outgrowth in sympathetic ganglia while nonpromoting structural congeners did not, in keeping with previous results in embryonic sensory ganglia. In contradistinction, promoters reversibly enhanced neurite outgrowth in malignant SH-SY5Y neuroblastoma cells, whereas nonpromoting congeners were inactive. The potent promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) reversibly increased the proportion of SH-SY5Y cells with neurites and the average length of neurites; the effects of the combination of TPA and NGF were greater than that of either compound alone. The half-maximum response to TPA was at about 2 ng/ml (3 nM). The neurites were thinner, straighter, and less branched and showed more swellings resembling beads or varicosities in comparison with NGF-induced neurites. TPA transiently inhibited the cellular growth rate between Days 2 and 4. Thereafter, the rate was the same as in untreated cultures. The transient inhibition was due to causes other than degradation of TPA since fresh TPA was added. The effect of TPA on neurite outgrowth was not transient and was independent of effects on growth. TPA also enhanced neurite outgrowth in another NGF responsive line, LA-N-5, but not in two unresponsive lines, CHP-100 and CHP-134.

Animals↗
PubMed1996

Distribution and functions of parathyroid hormone-related protein in vertebrate cells.

Parathyroid hormone-related protein (PTHrP) was isolated from tumors and identified as the agent of humoral hypercalcemia of malignancy (HHM) in 1987. Since then its gene structure in several mammalian and an avian species has been analyzed and its gene expression demonstrated in many adult and embryonic tissues derived from all three germ layers. The composition and structure of PTHrP peptide depends on both differential gene splicing and posttranslational processing, which result in a range of peptides of potentially diverse functions. This chapter describes the distribution of PTHrP in both normal and neoplastic adult and embryonic tissues. PTHrP is of fundamental importance to cell survival because the absence of the gene is fatal; this aspect of PTHrP function in cell physiology becomes overwhelmingly important in neoplasia. Intracrine or paracrine actions for PTHrP seem to be most likely in mammalian and avian physiology, but in fishes high circulating levels suggest classic endocrine functions as well. Much remains to be learned of the biology of this fascinating protein.

Amino Acid Sequence↗
PubMed1988

Inhibition of adhesion of F9 embryonal carcinoma cells to substratum by a novel monoclonal antibody, TEC-05, reactive with a developmentally regulated carbohydrate epitope.

Embryonal carcinoma cells carry on their surfaces carbohydrate antigens that are also expressed in early embryonic cells. We report here the expression and properties of a new developmentally regulated carbohydrate epitope, which is defined by a monoclonal antibody TEC-05. This antibody was generated by immunization of a rat with mouse embryonal carcinoma cells P19S1801A1. By immunofluorescence, the TEC-5 epitope was first detected on 8-cell-stage mouse embryos and was present on all subsequent stages of preimplantation development. Absorption analysis revealed that TEC-5 epitope was expressed only on a limited number of adult mouse tissues. In the direct radioantibody binding assay, TEC-05 reacted strongly with OTF9-63 cells and with some of the mouse embryonal carcinoma cell lines tested. Its reaction with differentiated cell lines was weak or undetectable. In the course of differentiation of OTF9-63 cells induced by retinoic acid, the epitope disappeared with the onset of morphological differentiation. The binding of the antibody to OTF9-63 cells was inhibited to 50% by 10-50 microM N-acetyllactosamine and lactose. Immunolabelling of extracts from OTF9-63 cells separated by sodium-dodecyl-sulfate (SDS) polyacrylamide gel electrophoresis revealed that TEC-5 epitope was carried by high-molecular-weight glycoconjugates (molecular weight greater than 100,000). Molecules, isolated from [3H]-fucose-labelled OTF9-63 cells by indirect immunoprecipitation with TEC-05 antibody, were degraded by extensive pronase digestion or mild alkaline treatment to large carbohydrate chains that were excluded from a Sephadex G-50 column. Direct evidence that TEC-05 antibody bound to embryoglycan was obtained using a modified Farr's assay. The antibody was found to inhibit adhesion of F9 and OTF9-63 cells to substratum. The inhibitory effect, which could be abrogated by lactose, seemed to be specific, because another IgM monoclonal antibody which also binds to embryoglycan had no effect. Combined data indicated that TEC-05 antibody recognizes a carbohydrate epitope which is involved in cell-substratum adhesion of F9 cells and which provides a new marker for structure-function studies of stage-specific embryonic antigens.

Animals↗
PubMed2006

Unsuccessful derivation of human embryonic stem cell lines from pairs of human blastomeres.

Human embryonic stem cells (hESC) that differentiate into all three primordial germ layers have been established. Differentiation of these cells into desirable lineages offers hope for future transplantation therapies. Currently, hESC lines are derived from the inner cell mass (ICM) of blastocysts, leading to destruction of the embryo, and thus the process is ethically controversial. Successful attempts at deriving hESC lines from blastomeres without destruction of the ensuing embryo have not been reported. One or two blastomeres are routinely biopsied from 8-cell embryos for preimplantation genetic diagnosis. In this study it was therefore attempted to derive hESC lines from paired blastomeres. Of 66 pairs of 8-cell stage blastomeres, four pairs produced two morula and two blastocyst-like structures. When plated on mitomycin-C-treated mouse embryonic fibroblasts, one morula and one blastocyst-like structure separately produced small colonies containing hESC-like cells with prominent nucleoli and high nuclear-cytoplasmic ratios. When these colonies were detached and plated onto fresh feeders, there was no further colony formation or ensuing hESC lines. The results showed that it might not be possible to derive hESC lines directly from paired blastomeres. A minimum number of blastomeres in close contact with one another may be required to successfully generate an hESC line as blastomeres, like ICM and hESC cells, may be 'social' cells.

Blastomeres↗
PubMed1998

The stage-specific expression of TEC-1, -2, -3, and -4 antigens on bovine preimplantation embryos.

The preimplantation developmental period is associated with constant changes within the embryo, and some of these changes are apparent on the embryo cell surface. For example, during transition from maternal to embryonic genome control and the compaction and differentiation of embryonic cells, the cell surface undergoes morphologic alterations that reflect changes in gene control. In order to gain insight into the events occurring during embryonic development and cellular differentiation, monoclonal antibodies specific for cell surface antigens (TEC antigens) of embryonic cells have been generated previously and shown to recognise either the carbohydrate moiety of embryoglycan or a developmentally regulated protein epitope. The TEC antigens have been identified on mouse preimplantation embryos, and their expression is specific to particular developmental stages. To determine whether these antigens are conserved in higher mammals, we examined the expression of four TEC antigens (TEC-1 to TEC-4) on in vitro-derived bovine and murine embryos during the preimplantation stage of development. It was found that bovine oocytes and embryos derived from in vitro maturation (IVM) and in vitro fertilisation (IVF) showed stage-specific expression of each of the TEC antigens investigated, with the pattern of expression overlapping but not identical to that seen in the mouse. Immunoprecipitation together with Western blot analysis showed that the TEC monoclonal antibodies recognised a single glycoprotein band with an apparent molecular weight of 70 kDa. Confocal microscopy of immunofluorescence staining of the bovine cells showed this protein to be located on the cell surface. The apparent negative expression of these TEC antigens by immunohistochemistry and immunoprecipitation at particular stages of development appears to be due to the epitopes being inaccessible to the TEC antibodies, since Western blotting revealed the TEC antigens to be present at all stages of development examined. Antibodies identifying stage-specific antigens will provide useful markers to characterise early embryonic cells, monitor normal embryonic development in vitro, and identify cell surface structures having a function in cell-cell interactions during embryogenesis and differentiation.

Animals↗
PubMed2003

Mouse embryonic mammogenesis as a model for the molecular regulation of pattern formation.

In this review we describe how mouse embryonic mammogenesis depends on a continuous communication between the epithelial and mesenchymal compartment of the mammary rudiment. Although the functions of only a few genes in the regulation of these epithelio-mesenchymal interactions during mouse mammary development are known so far, key roles are suggested for WNT, FGF and PTHrP signaling. However, the exact mechanism of action of these signaling pathways and their possible cross-talk in the induction of mammary development are not clear, nor does our current knowledge suffice to explain how the number and positions of the mammary rudiments are so well defined. Nonetheless, by the description of aberrant induction and/or maintenance of the mammary rudiments in a variety of inbred mouse strains and mutants, we have accumulated data demonstrating that the mammary rudiments develop independently of each other at these positions. In addition, each rudiment pair responds differently to altered levels of gene expression. This not only clarifies the unique identity of each placode, but the different molecular requirement of each placode also suggests that different molecular mechanisms may underlie the formation of such identical structures. For future investigations in the field, such a unique molecular identity of each mammary rudiment should be of critical concern.

Animals↗
PubMed2003

Derivation of embryonic germ cells and male gametes from embryonic stem cells.

Egg and sperm cells (gametes) of the mouse are derived from a founder population of primordial germ cells that are set aside early in embryogenesis. Primordial germ cells arise from the proximal epiblast, a region of the early mouse embryo that also contributes to the first blood lineages of the embryonic yolk sac. Embryonic stem cells differentiate in vitro into cystic structures called embryoid bodies consisting of tissue lineages typical of the early mouse embryo. Because embryoid bodies sustain blood development, we reasoned that they might also support primordial germ cell formation. Here we isolate primordial germ cells from embryoid bodies, and derive continuously growing lines of embryonic germ cells. Embryonic germ cells show erasure of the methylation markers (imprints) of the Igf2r and H19 genes, a property characteristic of the germ lineage. We show that embryoid bodies support maturation of the primordial germ cells into haploid male gametes, which when injected into oocytes restore the somatic diploid chromosome complement and develop into blastocysts. Our ability to derive germ cells from embryonic stem cells provides an accessible in vitro model system for studies of germline epigenetic modification and mammalian gametogenesis.

Animals↗
PubMedDate not supplied

Effects of cyproheptadine on the rat yolk sac membrane and embryonic development in vitro.

Electron-microscopic examinations of rat embryonic yolk sacs treated in vitro with 1.5 X 10(-5) M cyproheptadine showed proliferation of the lysosomal structures; other organelles remained unaffected, and also overall yolk-sac growth and vascularization were comparable to non-treated samples. Radioactive measurements with 125I-labelled albumin showed that yolk sacs and embryos of the cyproheptadine-treated group incorporated less radioactivity than the controls. Embryos inside the yolk sacs, treated either for 24 or 48 h, were severely retarded in growth and differentiation (approximately 50% of the controls). It is suggested that the specific action of cyproheptadine on yolk-sac lysosomal structures, combined with reduced macromolecular transport, is the cause of inhibited embryonic development.

Animals↗
PubMedDate not supplied

Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system.

Optical coherence tomography (OCT) is an emerging high-resolution real-time biomedical imaging technology that has potential as a novel investigational tool in developmental biology and functional genomics. In this study, murine embryos and embryonic hearts are visualized with an OCT system capable of 2-microm axial and 15-microm lateral resolution and with real-time acquisition rates. We present, to our knowledge, the first sets of high-resolution 2- and 3-D OCT images that reveal the internal structures of the mammalian (murine) embryo (E10.5) and embryonic (E14.5 and E17.5) cardiovascular system. Strong correlations are observed between OCT images and corresponding hematoxylin- and eosin-stained histological sections. Real-time in vivo embryonic (E10.5) heart activity is captured by spectral-domain optical coherence tomography, processed, and displayed at a continuous rate of five frames per second. With the ability to obtain not only high-resolution anatomical data but also functional information during cardiovascular development, the OCT technology has the potential to visualize and quantify changes in murine development and in congenital and induced heart disease, as well as enable a wide range of basic in vitro and in vivo research studies in functional genomics.

Animals↗
PubMed2004

Formation of partially ordered oligomers of amyloidogenic hexapeptide (NFGAIL) in aqueous solution observed in molecular dynamics simulations.

A combined total of more than 600.0 ns molecular dynamics simulations with explicit solvent have been carried on systems containing either four peptides or a single peptide to investigate the early-stage aggregation process of an amyloidogenic hexapeptide, NFGAIL (residues 22-27 of the human islet amyloid polypeptide). Direct observation of the aggregation process was made possible by placing four peptides in a box of water with an effective concentration of 158 mg/ml to enhance the rate of aggregation. Partially ordered oligomers containing multistrand beta-sheets were observed which could be the precursory structures leading to the amyloid-forming embryonic nuclei. Comparative simulations on a single peptide suggested that the combined effect of higher peptide concentration and periodic boundary condition promoted compact monomers and the short-range interpeptide interactions favored the beta-extended conformation. Of particular interest was the persistent fluctuation of the size of the aggregates throughout the simulations, suggesting that dissociation of peptides from the disordered aggregates was an obligatory step toward the formation of ordered oligomers. Although 95% of peptides formed oligomers and 44% were in beta-extended conformations, only 16% of peptides formed multistrand beta-sheets. The disordered aggregates were mainly stabilized by hydrophobic interactions while cross-strand main-chain hydrogen bonds manifested the ordered oligomers. The transition to the beta-extended conformation was mildly cooperative due to short-range interactions between beta-extended peptides. Taken together, we propose that the role of hydrophobic interaction in the early stage of aggregation is to promote disordered aggregates and disfavor the formation of ordered nuclei and dissociation of the disordered oligomers could be the rate-limiting step at the initiation stage.

Amyloid↗
PubMed2005

An alternative domain near the nucleotide-binding site of Drosophila muscle myosin affects ATPase kinetics.

In Drosophila melanogaster expression of muscle myosin heavy chain isoforms occurs by alternative splicing of transcripts from a single gene. The exon 7 domain is one of four variable regions in the catalytic head and is located near the nucleotide-binding site. To ascribe a functional role to this domain, we created two chimeric myosin isoforms (indirect flight isoform-exon 7a and embryonic-exon 7d) that differ from the native indirect flight muscle and embryonic body-wall muscle isoforms only in the exon 7 region. Germline transformation and subsequent expression of the chimeric myosins in the indirect flight muscle of myosin-null Drosophila allowed us to purify the myosin for in vitro studies and to assess in vivo structure and function of transgenic muscles. Intriguingly, in vitro experiments show the exon 7 domain modulates myosin ATPase activity but has no effect on actin filament velocity, a novel result compared to similar studies with other Drosophila variable exons. Transgenic flies expressing the indirect flight isoform-exon 7a have normal indirect flight muscle structure, and flight and jump ability. However, expression of the embryonic-exon 7d chimeric isoform yields flightless flies that show improvements in both the structural stability of the indirect flight muscle and in locomotor abilities as compared to flies expressing the embryonic isoform. Overall, our results suggest the exon 7 domain participates in the regulation of the attachment of myosin to actin in order to fine-tune the physiological properties of Drosophila myosin isoforms.

Actins↗
PubMed1998

Structural selectivity and molecular nature of L-glutamate transport in cultured human fibroblasts.

Uptake of L-[3H]glutamate by monolayers of fibroblasts cultured from human embryonic skin has been studied in the presence of several nonradioactive structural analogs of glutamate and aspartate. Results have suggested that the structural specificites of glutamate transporters in cultured human fibroblasts are similar to those of glutamate transporters in the mammalian brain. Only subtle differences have been detected: in the mammalian cerebral cortex, enantiomers of threo-3-hydroxyaspartate are almost equipotent as inhibitors of L-[3H]glutamate uptake while, in human fibroblasts, the D-isomer has been found to be an order of magnitude less potent than the corresponding L-isomer. Kinetic analysis of a model in which substrates are recognized by the glutamate transporter binding site(s) as both alpha- and beta-amino acids indicated that such a mechanism cannot explain the apparent negative cooperativity characterizing the effects of D- and L-aspartate. Molecular modeling has been used to estimate the optimum conformation of L-glutamate as it interacts with the transporter(s). Flow cytometry has indicated that all fibroblasts in culture express at least moderate levels of four glutamate transporters cloned from human brain. Small subpopulations (< 3%) of cells, however, were strongly labeled with antibodies against EAAT1 (GLAST) and EAAT2 (GLT-1) transporters. We conclude that these two transporters--known to be strongly expressed in brain tissue--can be principally responsible for the "high affinity" transport of glutamate also in nonneural cells.

ATP-Binding Cassette Transporters↗
PubMed2000

Xenopus laevis embryo development: arrest of epidermal cell differentiation by the chelating agent 1,10-phenanthroline.

The embryonic epidermis of stage 35 Xenopus laevis embryos is a highly differentiated structure composed of four cell types arranged in a regular architecture. Each type is distinguished by its distinct morphological characteristics. Some cells are ciliated (type 1); others have their surfaces covered by abundant, secreted vesicles of 0.1 microm diameter (type 2), or multiple linear aggregates of spherical subunits on their apical surfaces (type 3) or large secreted vesicles that emanate from prominent apical holes of 1 microm diameter (type 4). In contrast, the macroscopic appearance of embryos exposed to 10 microM 1,10-phenanthroline (OP) as well as the ultramicroscopic structure and organization of their epidermal cells are markedly altered. The most predominant cells of the embryonic epidermis are undifferentiated and of heterogeneous size. They lack any characteristic morphology and are arranged irregularly. Ghost cells are also identified. The recognizable differentiated cells are decreased in number and present in a scattered arrangement. These are identified as either type 1 or 2 cells but with ciliae that are shorter and thicker than control or with only a few vesicles larger than 0.1 microm in diameter on their surface. No cells with linear aggregates or prominent apical holes are identified. Except for the altered epidermis, the embryos do not develop any other major organs and exhibit axial abnormalities with an average dorso-anterior index of three. Thus, the chelating agent OP perturbs metal dependent processes essential for terminal differentiation that may likely account for the resultant abnormalities of embryo organogenesis and morphogenesis.

Animals↗
PubMed2007

Two-dimensional and three-dimensional time-lapse microscopic magnetic resonance imaging of Xenopus gastrulation movements using intrinsic tissue-specific contrast.

The amphibian embryo undergoes radical tissue transformations during blastula and gastrula stages, but live observation of internal morphogenetic events by optical microscopy is not feasible due to the opacity of the early embryo. Here, we report on the use of microscopic magnetic resonance imaging (MRI) to directly follow morphogenetic movements during blastula and gastrula stages of the Xenopus laevis embryo. We compare three different MRI modalities that take advantage of the intrinsic contrast present in embryonic tissues: three-dimensional (3D) fat-imaging, 3D water-imaging, and 2D high-speed high-resolution imaging of early embryonic stages. We show that the features revealed by the intrinsic contrast correlate with the histological structure of the embryo. Using this tissue specific intrinsic contrast, the main embryonic tissues and internal tissue movements as well as archenteron invagination can be differentiated without cell labeling. We present 2D and 3D time-lapse sequences of early Xenopus embryonic development, spanning the stages from early blastula to the end of gastrula, which show the complex internal rearrangements of gastrulation in essentially real-time.

Animals↗
PubMed2002

BetaIII tubulin-expressing neurons reveal enhanced neurogenesis in hippocampal and cortical structures after a contusion trauma in rats.

Neurogenesis is not only restricted to embryonic development, but also occurs in adult mammalian brains, including human. In this study, evidence is provided, that neurogenesis is involved in the repair of hippocampal and cortical structures after CNS injury. Cortical contusion was induced in 8-week-old Wistar rats. This trauma resulted in a primary cortical lesion and ipsilateral distant remote hippocampal damage, involving primarily CA3-pyramidal cells. The progression of injury was followed over a time course of 7 days, using Nissl-staining and a monoclonal antibody against betaIII tubulin-a specific marker for neurogenic cells. Nissl staining showed a partial recovery of damaged cortical and hippocampal cells at day 7. This recovery was accompanied by an increase of neurogenic cells in these structures, particularly in the dentate gyrus and the neocortical areas. Taken together, these findings provide evidence for the involvement of neurogenesis in the repair processes after traumatic brain injury.

Animals↗
PubMed1984

Ultrastructural and immunofluorescence studies of basal-lamina alterations during mouse-lung morphogenesis.

Epithelial differentiation during lung development appears to be influenced by mesenchyme-derived instructions coupled with hormonal regulations. The basal lamina which is associated with progenitor and differentiating epithelia during mouse embryogenesis (Theiler-stages 16-28) was examined by transmission electron microscopy and indirect-immunofluorescence microscopy. During the embryonic phase of lung development, progenitor epithelia for the pulmonary acinus projected microvilli or cytoplasmic "feet" through the basal lamina, which resulted in discontinuities and a close approximation of the adjacent mesenchymal-cell processes. These changes were also associated with the transitory polarization of mesenchymal cells perpendicular to the plane of the basal lamina, which resulted in a sheet of cuboidal mesenchymal cells adjacent to the developing acinar-tubule epithelium. During the embryonic phase of lung development, these specific interstitial or mesenchymal cells stained for heparan-sulfate proteoglycans; no other cell types were immunostained. By Theiler-stage 25, the acinar-tubule epithelia had differentiated into type-II pneumonocytes which contained lamellar bodies and significant amounts of glycogen. Fibronectin, laminin, and heparan-sulfate proteoglycan were localized in the basement membranes during the embryonic, canalicular, and terminal sac phases of lung morphogenesis. A diffuse localization of fibronectin of the interstitial cell surfaces was observed. These observations indicate that major changes in the structure and composition of basal lamina occur during the embryonic and fetal phases of pulmonary-acinus epithelial-cell differentiation and the production of pulmonary surfactant. The major changes in the basal lamina may be partly mediated by mesenchyme-derived instructions for type-II epithelial-cell differentiation.

Animals↗
PubMed1983

Poly(A) RNA of the egg cytoplasm: structural resemblance to the nuclear RNA of somatic cells.

This paper concerns the structural characteristics of the poly(A) RNA stored in unfertilized amphibian and echinoderm eggs. Though located in the egg cytoplasm, at least two-thirds of these maternal transcripts display an interspersed sequence organization similar to that of nuclear RNA. In Xenopus laevis interspersed poly(A) RNA molecules are synthesized and deposited in the oocyte cytoplasm throughout the main growth phase of oogenesis. Regions of the sea urchin genome that are represented by interspersed maternal transcripts have been recovered from recombinant clone libraries. In one case the same single-copy sequence is found both in an abundant message-sized 1.6 kilobase (kb) maternal transcript and in a 7.5 kb maternal transcript that structurally resembles a precursor form and is not found in embryonic polysomes. In a second example considered, a 9.5 kb transcript was identified in embryo nuclear RNA that may be identical in structure with an interspersed maternal poly(A) RNA derived from the same transcription unit. Transcription of this sequence appears to be constitutive in somatic cell nuclei, though no homologous cytoplasmic RNAs are found after early cleavage. This may be a widespread form of regulation for transcription units expressed in female germ cells, and represented in the maternal poly(A) RNA pools of unfertilized eggs.

Animals↗
PubMed1984

Pathogenesis of idiopathic clubfoot.

During embryonic development the foot passes consecutively into three different positions: (1) when the embryo is in the 15-mm stage the foot is in a straight line with the leg (initial position); (2) by 30 mm the foot passes to a marked equinovarus-adductus position (embryonic position); and (3) finally, by 50 mm, the foot changes to a slightly equinovarus adductus position (fetal position). The morphologic and structural changes of the foot from the initial to the embryonic position result from the growth of the distal ends of the fibula and of the skeletal elements of the lateral foot during the "fibular phase" of rapid growth (from 21 to 30 mm). The changes from the embryonic to the fetal position are due to the growth of the distal ends of the tibia and of the skeletal rays of the medial foot during the "tibial phase" of rapid growth. Many known noxious industrial chemicals (and probably many more yet to be recognized) have antimitotic and antimetabolic action. Depending on the characteristics of the chemical, some produce permanent arrest and therefore congenital malformation, while others cause temporary growth arrest, e.g., Harris transverse lines, which is frequently unnoticed. Finally, some substances, e.g., glucocorticoids, cause a growth delay. Depending on the developmental stage of the embryo and the duration of the action of the noxious substance, growth arrest of the foot occurs in an attitude close to the embryonic position. If it occurs at the end of the fibular phase and during the first half of the tibial phase, the foot will remain in a permanent and marked equinovarus-adductus position, and a severe clubfoot will result. When a noxious chemical acts only during the last half of the tibial phase, a mild, flexible clubfoot will result because by this stage most parts of the embryonic components have been corrected. If it occurs at the end of the tibial phase, a simple metatarsus adductus deformity will persist. As soon as the growth arrest phase ends, all of the skeletal elements begin to grow again, but only from a later point in development. If the growth disturbance occupies the entire tibial phase, neither the tibia nor the skeletal elements of the foot would be able to complete a rapid growth spurt, since by that stage the moment genetically programmed for such growth has already passed. The morphology of the deformities existing in the clubfoot corresponds to the morphologic program of the embryonic foot.(ABSTRACT TRUNCATED AT 400 WORDS)

Clubfoot↗