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D Sassoon

Publications and source records attributed to D Sassoon.

At least 37 records · Page 2Linked to original sources
PubMed1992

A transgene target for positional regulators marks early rostrocaudal specification of myogenic lineages.

In transgenic mice, muscle-specific regulatory elements from the myosin light chain (MLC) 1/3 locus drive graded expression of a linked CAT reporter gene in selected fast muscles along the anteroposterior axis of the adult animal. The gradient of MLC-CAT transcripts is established early in development, during the generation of somites from the paraxial mesoderm and the activation of myogenic factor gene expression, and is not reflected in the expression of the endogenous MLC1 gene. At later embryonic stages, the gradient of MLC-CAT transcripts persists in intercostal and intervertebral muscles, but is not maintained in other axial muscles. Profiles of CAT transgene activity reveal that the gradient is generated during the maturation of increasingly caudal somites, opposite to the direction of somite development, and is retained in dissociated somite cultures. We propose that coexpression of myogenic factors is necessary but not sufficient to regulate expression of the MLC-CAT transgene, which is responsive to additional positional cues in the embryo.

Animals↗
PubMed1992

Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with retinoic acid receptor mRNA localization.

We report results from a study of Hox-7 expression during mouse embryonic and fetal development and compare the localization of Hox-7 transcripts with those of the retinoic acid receptors. Transcripts were detected by in situ hybridization. Hox-7 expression occurs in (1) cephalic neural crest and its derivatives, (2) sites of ectomesodermal interaction, (3) extraembryonic tissues, and (4) endocardial cells. Hox-7 does not seem to be involved in defining rostrocaudal boundaries, but instead appears to be expressed along the proximodistal axes at these sites. We further investigated the active sites of morphogenesis, which involve an ectomesodermal interaction (e.g., limb buds, visceral arches), including genital tubercle and tail ridge. These are regions highly positive for Hox-7 transcripts, and many are known to be sites for the expression of gamma-retinoic acid receptors (RARs) and cellular retinoic acid binding proteins. Most regions that express Hox-7 are subregions of gamma-RAR expression. In the developing limb bud, expression of Hox-7 takes place in the interdigital region, where it overlaps areas of beta-RAR expression.

Animals↗
PubMed1992

Molecular aspects of regeneration in developing vertebrate limbs.

We review embryological as well as molecular evidence that emphasizes the idea that both the regenerate and the developing vertebrate limb bud utilize a similar set of signals that regulate pattern formation. Evidence is presented to implicate the Hox-7.1 gene in the developmental regulation of growth, differentiation, and positional assignment during limb outgrowth and the proposal is made that the expression of this gene governs the cellular activities within the progress zone during limb outgrowth. Finally, we review the limited information known about the regenerative capabilities of limb buds in organisms that cannot regenerate as adults. We content that a solution to the problem of regenerative failure among higher vertebrates will come progressively through a stepwise analysis of impaired regeneration associated with increasing developmental age.

Animals↗
PubMed1992

[Multicentric study of 143 cases of resection of the proximal carpal bones].

Proximal row carpectomy is an old procedure but the good results published in the literature, it still has bad reputation. The authors conducted a retrospective multicentric study in 143 patients, 128 of whom were post-traumatic cases. And results were good in terms of pain relief. Increase in grip strength was observed in 80% of cases. Wrist range of motion was not improved by resection. The results were not predicted by preoperative status. No prognostic factor could be defined on the basis of study.

Adolescent↗
PubMed1992

In-situ hybridization of tropoelastin mRNA during the development of the multilayered neonatal rat aortic smooth muscle cell culture.

Cultured neonatal rat aortic smooth muscle cells are active in synthesizing and depositing large amounts of elastin in their extracellular matrix, making this an ideal system for studying elastogenesis. In this study, the ability of individual cells to synthesize tropoelastin was examined by in-situ hybridization methods. One-micron semi-thin epoxy resin-embedded transverse sections of cells cultured 1, 2, 3 and 4 weeks showed an increase with time in both the number of cells with hybridization signal and the signal intensity; tropoelastin mRNA hybridization signal intensity decreased thereafter up to 8 weeks in culture. In longitudinal sections through the early cultures (1-week), we observed mitotic cells with no detectable hybridization signal, and non-mitotic cells with either no, little or high signal intensity. These data suggest that mitotic cells do not synthesize tropoelastin, and that there is a strong correlation between the hybridization signal intensity and the rate of tropoelastin synthesis. These data also suggest in-situ hybridization methods can detect which cell(s) contain tropoelastin mRNA, their location in the multilayer, and variations in signal intensity. We conclude it is possible to correlate hybridization signal intensity with variations of tropoelastin mRNA levels within individual cells of the cultured smooth muscle cell multilayer.

Animals↗
PubMed1992

Expression of muscle genes in the mouse embryo.

Using isogene specific probes and in situ hybridization on sections, we have examined the expression of structural and regulatory genes in the mouse embryo during the formation of cardiac and skeletal muscle. The temporal and spatial information thus obtained about the onset of expression of muscle genes provides insight into the regulation of myogenesis in vivo. Actin and myosin sequences present in different compartments of the adult heart are initially all co-expressed in the cardiac tube (between 7-8 days). The process of spatial restriction to atrial or ventricular compartments of the heart takes place asynchronously later. In contrast, the onset of expression of actin and myosin genes in the first skeletal muscle, the myotome, which corresponds to the central compartment of the somite, as well as their subsequent down-regulation in different skeletal muscle masses, takes place very asynchronously. One might predict that factor(s) responsible for the transcriptional activation of these genes are present in sufficient quantity in the cardiac tube, whereas in skeletal muscle individual genes are responding to variable levels of factor(s). In fact the four myogenic regulatory sequences present in the mouse - MyoD1, myogenin, myf-5 and myf-6 - do show distinct patterns of expression during the development of skeletal muscle. None of these sequences have been detected in the heart. In the myotome there is no general correlation between the appearance of a particular myogenic sequence and the activation of a particular structural gene. A striking example of this is provided by the muscle isoform of creatine phosphokinase. We would propose that each muscle structural gene has a different threshold of activation, depending on the quantity and nature of the myogenic factor present. We have also examined the onset of expression of the X-linked dystrophin gene known to be expressed in adult heart and skeletal muscle. In the myotome dystrophin transcripts are first detected at the time when myosin heavy chains first accumulate and muscular contraction is initiated. In contrast in the cardiac tube dystrophin transcripts are not detected initially, at a time (from 8 days) when the heart contracts. This observation can be correlated with the pathology of the disease which points to a more essential role of dystrophin in skeletal muscle. No muscle structural gene examined is expressed in the somite prior to myotome formation. If the myogenic regulatory sequences are implicated in muscle cell determination then they should be expressed in the dermomyotome of the immature somite which gives rise to muscle precursor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1990

The expression of myosin genes in developing skeletal muscle in the mouse embryo.

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and accumulation. The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development.

Animals↗
PubMed1990

Developmental regulation of myosin gene expression in mouse cardiac muscle.

Expression of the two isoforms of cardiac myosin heavy chain (MHC), MHC alpha and MHC beta, in mammals is regulated postnatally by a variety of stimuli, including serum hormone levels. Less is known about the factors that regulate myosin gene expression in rapidly growing cardiac muscle in embryos. Using isoform-specific 35S-labeled cRNA probes corresponding to the two MHC genes and the two myosin alkali light chain (MLC) genes expressed in cardiac muscle, we have investigated the temporal and spatial pattern of expression of these different genes in the developing mouse heart by in situ hybridization. Between 7.5 and 8 d post coitum (p.c.), the newly formed cardiac tube begins to express MHC alpha, MHC beta, MLC1 atrial (MLC1A), and MLC1 ventricular (MLC1V) gene transcripts at high levels throughout the myocardium. As a distinct ventricular chamber forms between 8 and 9 d p.c., MHC beta mRNAs begin to be restricted to ventricular myocytes. This process is complete by 10.5 d p.c. During this time, MHC alpha mRNA levels decrease in ventricular muscle cells but continue to be expressed at high levels in atrial muscle cells. MHC alpha transcripts continue to decrease in ventricular myocytes until 16 d p.c., when they are detectable at low levels, but then increase, and finally replace MHC beta mRNAs in ventricular muscle by 7 d after birth. Like MHC beta, MLC1V transcripts become restricted to ventricular myocytes, but at a slower rate. MLC1V mRNAs continue to be detected at low levels in atrial cells until 15.5 d p.c. MLC1A mRNA levels gradually decrease but are still detectable in ventricular cells until a few days after birth. This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development.

Aging↗
PubMed1990

Uterine leiomyomas in pregnancy: a prospective study.

Uterine leiomyomas are associated with various complications during pregnancy. During a 2-year period, pregnant women with a history of leiomyomas were referred to our antenatal testing unit for ultrasound evaluation. Eighty-five patients were found to have single or multiple leiomyomas by ultrasound examination. The size (total leiomyoma volume), number, and location of the leiomyoma(s) were ascertained. Each woman with leiomyoma(s) was matched by age, race, and parity with one without leiomyomas. Both groups were followed throughout pregnancy, and outcomes were compared. Size, number, or location of the leiomyoma had no influence on outcome. Student t test indicated a significantly (P less than .01) lower mean gestational age at the time of delivery in women with leiomyomas.

Adult↗
PubMed1989

Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis.

MyoD1 and myogenin are muscle-specific proteins which can convert non-myogenic cells in culture to differentiated muscle fibres, implicating them in myogenic determination. The pattern of expression of MyoD1 and myogenin during the early stages of muscle formation in the mouse embryo in vivo and in limb-bud explants cultured in vitro, indicates that they may have different functions in different types of muscle during development.

Animals↗
PubMed1989

The protein encoded by a murine male germ cell-specific transcript is a putative ATP-dependent RNA helicase.

The murine PL10 cDNA corresponds to a transcript expressed only in the male germ line. Its expression is developmentally regulated, with high levels of transcripts being present during the meiotic and haploid stages of spermatogenesis. The deduced protein is shown to be highly homologous to the murine translation initiation factor eIF-4A and to other proteins that are also homologous to eIF-4A, including the Drosophila protein vasa. By consensus sequence conservation and comparison of secondary structure predictions, putative mononucleotide binding and DNA/RNA binding domains are proposed to be shared by all these proteins. Taken together, these results suggest a helicase function for PL10 protein similar to that of eIF-4A and suggests its possible role in a key step of the spermatogenic process. The possible significance of the similarity between the PL10 protein and the protein product of the maternal effect gene vasa is also discussed.

Amino Acid Sequence↗
PubMed1989

Hox-7, a mouse homeobox gene with a novel pattern of expression during embryogenesis.

A new mouse Hox locus, Hox-7, is defined on chromosome 5 by a gene homologous to the Drosophila gene msh, which contains a homeobox sequence distantly related to that of Antennapedia. By in situ hybridization, expression of Hox-7 is detected in the neural fold of embryos, and also in cephalic neural crest. In addition, expression takes place in the developing valves of the embryonic heart. Mandibular and hyoid arches are strongly labelled, expression becoming restricted to the most distal part of mouth and face processes as development proceeds. Intense labelling is also observed in developing limb buds, in the distal region which has been shown to be essential for limb morphogenesis. The pronounced accumulation and regional localization of Hox-7 transcripts in mandibular and limb processes point to a specific morphogenetic role for this mouse homeobox gene.

Amino Acid Sequence↗
PubMed1989

A developmental study of the abnormal expression of alpha-cardiac and alpha-skeletal actins in the striated muscle of a mutant mouse.

BALB/c mice possess a 5' duplication of the alpha-cardiac actin gene which is associated with abnormal levels of alpha-cardiac and alpha-skeletal actin mRNAs in adult cardiac tissue. This mutation therefore provides a potential tool for the study of the inter-relationship between the striated muscle actins. We have examined the expression of this actin gene pair throughout the development of skeletal and cardiac muscle in BALB/c mice. During embryonic and fetal development, the expression of these two genes is indistinguishable from that in normal mice, as determined by in situ hybridization. A quantitative postnatal study demonstrates that in the hearts of normal mice the level of alpha-cardiac actin mRNA declines, whereas that of alpha-skeletal actin increases. In mutant mice, these trends are exaggerated so that whereas normal mice have 95.8% alpha-cardiac mRNA and 4.2% alpha-skeletal mRNA in the adult heart, BALB/c mice have 52.4 and 47.6% of these mRNAs, respectively. This difference is also reflected at the protein level. In developing skeletal muscle, the expression of these genes follows kinetics similar to that observed in the heart with a decrease in the relative level of alpha-cardiac mRNA as the muscle matures. Cardiac actin mRNA levels are again lower in the mutant mouse, but here the effect is less striking because skeletal actin is the predominant isoform. These results are discussed in the context of the interaction between this actin gene pair in developing and adult striated muscle.

Actins↗
PubMed1989

Development and hormone regulation of androgen receptor levels in the sexually dimorphic larynx of Xenopus laevis.

Development of the sexually dimorphic larynx in African clawed frogs is controlled by secretion of androgenic steroids (D. Sassoon and D. Kelley, 1986, Amer. J. Anat. 177, 457-472). Adult laryngeal muscle shows high levels of androgen binding relative to other skeletal muscles and binding activity in males is three times that in females (N. Segil, L. Silverman, and D. Kelley, 1987, Gen. Comp. Endocrinol. 66, 95-101). To determine when androgen sensitivity and sex differences arise, we assayed [3H]dihydrotestosterone (DHT) binding activity in larynges from metamorphic and postmetamorphic male and female frogs. Scatchard analyses indicate that DHT binds to a saturable component with high affinity. At metamorphosis, male and female juveniles have average binding levels of 262 and 269 fmoles/mg protein, respectively, approximately 7 to 20 times their adult values. At 3 months postmetamorphosis (PM), sexually dimorphic binding levels are observed. Binding activity declines gradually in females from metamorphosis to 9 months PM. In males, levels of binding activity remain high throughout the first 6 months PM and then decrease to near adult levels by 9 months PM. Administration of exogenous DHT to 3 months PM juveniles decreases average binding activity from 180 (male) or 74 fmoles/mg (female) to 33.5 fmoles/mg in both sexes. Testosterone has a less pronounced effect on binding activity in males than DHT and is ineffective in females. We conclude that sexually dimorphic adult levels of androgen binding in larynx arise by differential decrease from initially high, sexually monomorphic levels and that high titers of circulating androgens normally present by 6 months PM in males are responsible for the marked decrease in binding activity observed during laryngeal development.

Androgens↗
PubMed1989

Nonsynchronous accumulation of alpha-skeletal actin and beta-myosin heavy chain mRNAs during early stages of pressure-overload--induced cardiac hypertrophy demonstrated by in situ hybridization.

The development of cardiac hypertrophy secondary to pressure overload is accompanied by isoformic changes of contractile proteins such as myosin and actin. 35S-Labeled complementary RNA (cRNA) probes and in situ hybridization procedures were used for analysis of the regional distribution of newly formed transcripts from alpha-skeletal actin (alpha-sk-actin) and beta-myosin heavy chain (beta-MHC) genes during the early stages of pressure overload. The study was performed in 25-day-old rats submitted to a thoracic aortic stenosis and killed after surgery at times ranging from 4 hours to 3 days. Neither alpha-sk-actin nor beta-MHC messenger RNA (mRNA) was detected in the hearts of normal and sham-operated animals. However, alpha-sk-actin mRNA accumulated throughout the entire left ventricle as early as 4 hours after aortic stenosis, and by 12 hours was also detected in the left atrium. In contrast, beta-MHC mRNA was hardly detectable before day 1, and by days 2-3 was mainly restricted to the inner part of the left ventricle and around the coronary arteries. The absence of spatial and temporal coordination in the accumulation of alpha-sk-actin and beta-MHC mRNAs indicates that different signals and/or regulatory mechanisms are implicated in the induction of the two genes in response to hemodynamic overload.

Actins↗
PubMed1988

Structure and sequence of the myosin alkali light chain gene expressed in adult cardiac atria and fetal striated muscle.

Mammalian cardiac muscle contains two myosin alkali light chains which are the major isoforms present in either atrial (MLC1A) or ventricular (MLC1V) muscle, and which are different from the fast skeletal muscle isoforms (MLC1F and MLC3F). The atrial isoform is also expressed in fetal skeletal and fetal ventricular muscle, where this isoform is also described as the fetal isoform MLC1emb. We have previously isolated a cDNA clone encoding part of the mouse MLC1A/MLC1emb isoform and have used this clone to demonstrate the identity of MLC1A and MLC1emb in the mouse. To date no information on the amino acid sequence of this mammalian atrial/fetal isoform has been available. Here we present the complete structure and sequence of the mouse MLC1A/MLC1emb gene, together with the predicted amino acid sequence of this isoform. Comparison of the MLC1A/MLC1emb gene and polypeptide with those of MLC1F and MLC1V suggests that MLC1A/MLC1emb and MLC1V were generated from a common ancestral gene. The NH2-terminal region of MLC1A/MLC1emb, thought to be involved in the actomyosin interaction, shows conservation with MLC1V but not with MLC1F suggesting a shared functional domain in these cardiac isoforms. Comparison with the chicken embryonic MLC (L23) suggests that although MLC1A/MLC1emb and L23 show very different patterns of expression, both during development and in the adult, they probably represent the homologous gene in these two species.

Amino Acid Sequence↗
PubMed1988

Detection of the nicotinic acetylcholine receptor alpha-subunit mRNA by in situ hybridization at neuromuscular junctions of 15-day-old chick striated muscles.

In adult vertebrate striated muscle, the nicotinic acetylcholine receptor (AChR) is almost exclusively localized in the postsynaptic membrane of the neuromuscular junction. Using in situ hybridization, we show that, in two different chicken muscles [the slow multi-innervated anterior latissimus dorsi (ALD) and the fast singly innervated posterior latissimus dorsi (PLD)], the AChR alpha-subunit mRNA is detected at discrete regions on myofibres and that these regions co-localize (80% correspondence) with neuromuscular junctions identified by histochemical staining for acetylcholinesterase. Moreover, autoradiographic grains densely accumulate on and around subsynaptic nuclei. In contrast, hybridization with an actin probe results in a strong signal distributed over the entire length of the myofibres. Denervation increases the level of AChR alpha-subunit mRNA both in the PLD and to a lesser extent in the ALD. By in situ hybridization we observe that, although a perinuclear pattern is maintained, the labelled nuclei appear randomly distributed among approximately 10% of the nuclei. These results are discussed in a model of AChR gene expression in vertebrate striated muscle fibres.

Acetylcholinesterase↗