The role of morphogenetic cell death during abnormal limb-bud outgrowth in mice heterozygous for the dominant mutation Hemimelia-extra toe (Hmx)

Development ◽  
1981 ◽  
Vol 65 (Supplement) ◽  
pp. 289-307
Author(s):  
T. B. Knudsen ◽  
D. M. Kochhar

A dominant mutation in the mouse, Hemimelia-extra toe (Hmx), induces congenital limb malformations in heterozygotes. Typical expression includes axial shortening of the radius, tibia and talus (‘hemimelia’), with supernumerary metacarpals, metatarsals, and digits (‘polydactyly’). Pathogenesis was investigated during developmental stages 16 through 22 (1lth through 15th days of gestation). Full expression was apparent during stage 20 when the limb pattern was comprised of pre-cartilaginous anlagen. Formation of a pre-axial protrusion on the autopod during stage 17 or 18 was the earliest gross abnormality, and foreshadowed the development of supernumerary digits. Microscopically, there was an alteration in the pattern of physiologic cellular degeneration (PCD) programmed to occur within the zeugopod and autopod. The ‘opaque patch’ (mesodermal necrotic zone normally occurring between tibial and fibular anlagen) was overextended pre-axially causing resorption of the tibial precartilage. Additionally, PCD normally occurring within the basal cell layer of the apical ectodermal ridge (AER) and the ‘foyer primaire préaxial’ was not expressed in the mutant autopod. This occurred in association with outgrowth of the protrusion. The pre-axial portion of the AER remained in an abnormally thickened, viable, proliferative state, and did not undergo scheduled degression. This may have been the basis for prolonged induction of pre-axial outgrowth. Paucity of mesenchymal cell filopodial processes extended along the basal lamina, as well as a rarefaction of the filamentous material normally associated with the mesodermal face of the basal lamina, was detected at the pre-axial AER-mesenchymal interface on stage 18. A potential involvement of epithelial-mesenchymal interactions in the induction of epithelial PCD is discussed.

1983 ◽  
Vol 61 (8) ◽  
pp. 967-979 ◽  
Author(s):  
R. J. Van Exan ◽  
B. K. Hall

The initiation of osteogenesis at 7 days in the embryonic chick mandibular mesenchyme depends on an epithelial induction in the mandible to day 4. This article reviews a series of experiments conducted to study the nature of this inductive mechanism. Transfilter tissue recombinations were used to determine whether direct tissue apposition was required for induction. Ultrastructural studies of the epithelial–mesenchymal interface were conducted to see if direct epithelial–mesenchymal cell–cell contacts occurred during the inductive stage in vivo. Epithelial cells were cultured on Millipore filters for 28 days and allowed to deposit extracellular products. These products were tested for inductive activity. Findings from these three sets of experiments were discussed with respect to the inductive mechanism. Our results indicate that the induction is not mediated by a diffusible substance and that direct apposition of the two tissues is required. The mechanism of induction, however, does not require direct epithelial–mesenchymal cell to cell contacts. This suggests that a nondiffusible component of the extracellular matrix may be involved. Epithelial extracellular products are inductively active and have the appearance of basal lamina. The active component of the extracellular product is proteinaceous, perhaps collagen, and appears to be situated in the epithelial basal lamina. The role of basal lamina in epithelial–mesenchymal interactions is discussed.


Development ◽  
1982 ◽  
Vol 68 (1) ◽  
pp. 69-86
Author(s):  
Linwood M. Sawyer

The fine structure of the normal and wingless chick limb bud was examined with scanning and transmission electron microscopy. The apical ectodermal ridge (AER) of the normal limb bud was composed of pseudostratined columnar cells. These cells contained gap junctions, electron-dense vesicles, and numerous microtubules and microfilaments that were oriented perpendicularly to the basal lamina. Microfilaments were also found coursing transversely in the basal cell cytoplasm. The ectoderm of the wingless mutant limb bud lacked a well-developed AER and resembled the dorsal and ventral ectoderm of the normal embryo. Gap junctions and electron-dense vesicles found in the AER of the normal limb bud were not apparent in the mutant ectoderm. The normal-limb bud mesoderm is composed of stellate cells that are oriented at right angles to the overlying ectoderm. There is a prominent subectodermal space that is traversed by numerous mesenchymal cell filopodia. The mesodermal cells of the mutant limb bud are compact and round and have short stubby filopodia, while the cells of the adjacent flank mesoderm are stellate. The subectodermal space is absent and the mesodermal cells are in intimate association with the basal lamina of the overlying ectoderm. Ruthenium red was employed as an extracellular marker for glycosaminoglycan$. No differences were found in the distribution of these substances in normal and mutant limb buds. In severalcases the basal lamina of the mutant limb bud ectoderm was discontinuous aqd the lamina lucida wasnot apparent. The results indicate that the mutation has an effect on the limb buds' ability to maintain a well-developed AER and basal lamina. It also suggest$ that the wingless gene affects the shape and possibly the mobility of the limb-bud mesoderm cells.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Li ◽  
Zaichao Zheng ◽  
Hongyu Li ◽  
Rongrong Fu ◽  
Limei Xu ◽  
...  

AbstractDespite the central role of hemocytes in crustacean immunity, the process of hemocyte differentiation and maturation remains unclear. In some decapods, it has been proposed that the two main types of hemocytes, granular cells (GCs) and semigranular cells (SGCs), differentiate along separate lineages. However, our current findings challenge this model. By tracking newly produced hemocytes and transplanted cells, we demonstrate that almost all the circulating hemocytes of crayfish belong to the GC lineage. SGCs and GCs may represent hemocytes of different developmental stages rather than two types of fully differentiated cells. Hemocyte precursors produced by progenitor cells differentiate in the hematopoietic tissue (HPT) for 3 ~ 4 days. Immature hemocytes are released from HPT in the form of SGCs and take 1 ~ 3 months to mature in the circulation. GCs represent the terminal stage of development. They can survive for as long as 2 months. The changes in the expression pattern of marker genes during GC differentiation support our conclusions. Further analysis of hemocyte phagocytosis indicates the existence of functionally different subpopulations. These findings may reshape our understanding of crustacean hematopoiesis and may lead to reconsideration of the roles and relationship of circulating hemocytes.


Author(s):  
Millissia Ben Maamar ◽  
Eric E Nilsson ◽  
Michael K Skinner

Abstract One of the most important developing cell types in any biological system is the gamete (sperm and egg). The transmission of phenotypes and optimally adapted physiology to subsequent generations is in large part controlled by gametogenesis. In contrast to genetics, the environment actively regulates epigenetics to impact the physiology and phenotype of cellular and biological systems. The integration of epigenetics and genetics is critical for all developmental biology systems at the cellular and organism level. The current review is focused on the role of epigenetics during gametogenesis for both the spermatogenesis system in the male and oogenesis system in the female. The developmental stages from the initial primordial germ cell through gametogenesis to the mature sperm and egg are presented. How environmental factors can influence the epigenetics of gametogenesis to impact the epigenetic transgenerational inheritance of phenotypic and physiological change in subsequent generations is reviewed.


Teratology ◽  
2002 ◽  
Vol 66 (6) ◽  
pp. 288-299 ◽  
Author(s):  
Chunwei Huang ◽  
Barbara F. Hales
Keyword(s):  

2002 ◽  
Vol 48 (4) ◽  
pp. 526-552 ◽  
Author(s):  
Barbara Bloom ◽  
Barbara Owen ◽  
Elizabeth Piper Deschenes ◽  
Jill Rosenbaum

This article reports findings from a survey of officials from various California state agencies and a series of interviews and focus groups with female youth and professionals serving this population. The study examined types of services provided, program barriers, and facilitation of change. The findings were used to make gender-specific policy and program recommendations. The authors found that meeting the needs of girls and young women requires specialized staffing and training, particularly in terms of relationship and communication skills, gender differences in delinquency, substance abuse education, the role of abuse, developmental stages of female adolescence, and available programs and appropriate placements and limitations. Effective programming for girls and women should be shaped by and tailored to their real-world situations and problems. In order to do this, a theoretical approach to treatment that is gender-sensitive and that addresses the realities of girls' lives must be developed.


2004 ◽  
Vol 379 (2) ◽  
pp. 283-289 ◽  
Author(s):  
Marie-Chloé BOULANGER ◽  
Tina Branscombe MIRANDA ◽  
Steven CLARKE ◽  
Marco di FRUSCIO ◽  
Beat SUTER ◽  
...  

The role of arginine methylation in Drosophila melanogaster is unknown. We identified a family of nine PRMTs (protein arginine methyltransferases) by sequence homology with mammalian arginine methyltransferases, which we have named DART1 to DART9 (Drosophilaarginine methyltransferases 1–9). In keeping with the mammalian PRMT nomenclature, DART1, DART4, DART5 and DART7 are the putative homologues of PRMT1, PRMT4, PRMT5 and PRMT7. Other DART family members have a closer resemblance to PRMT1, but do not have identifiable homologues. All nine genes are expressed in Drosophila at various developmental stages. DART1 and DART4 have arginine methyltransferase activity towards substrates, including histones and RNA-binding proteins. Amino acid analysis of the methylated arginine residues confirmed that both DART1 and DART4 catalyse the formation of asymmetrical dimethylated arginine residues and they are type I arginine methyltransferases. The presence of PRMTs in D. melanogaster suggest that flies are a suitable genetic system to study arginine methylation.


Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 89-108
Author(s):  
Carla Falugi ◽  
Margherita Raineri

The distribution of acetylcholinesterase (AChE) and pseudocholinesterase (BuChE) activities was studied by histochemical, quantitative and electrophoretical methods during the early development of chick limbs, from stage 16 to stage 32 H.H. (Hamburger & Hamilton, 1951). By quantitative methods, true AChE activity was found, and increased about threefold during the developmental period, together with a smaller amount of BuChE which increased more rapidly in comparison with the AChE activity from stage 25 to 32 H.H. Cholinesterase activity was histochemically localized mainly in interacting tissues, such as the ectoderm (including the apical ectodermal ridge) and the underlying mesenchyme. True AChE was histochemically localized around the nuclei and on the plasma membrane of ectodermal (including AER) and mesenchymal cells, and at the plasma membrane of mesenchymal cell processes reaching the basal lamina between the ectoderm and the mesenchyme. AChE together with BuChE activity was found in the basal lamina between the ectoderm and the mesenchyme, in underlying mesenchymal cells and in deeper mesenchymal cells, especially during their transformation into unexpressed chondrocytes. During limb morphogenesis, the cellular and regional localization of the enzyme activities showed variations depending on the stage of development and on the occurrence of interactions. The possibility of morphogenetic functions of the enzyme is discussed.


Development ◽  
1986 ◽  
Vol 94 (1) ◽  
pp. 267-275
Author(s):  
C. P. Cottrill ◽  
Paul T. Sharpe ◽  
Lewis Wolpert

A technique which identifies cells differing in surface character, aqueous two-phase partition using thin-layer countercurrent distribution (TLCCD), has been used to study differentiation and pattern formation in the developing chick limb bud. The TLCCD profiles of cell populations, derived from various regions of morphologically undifferentiated mesenchyme from three different stages of limb development, have been compared. At no stage, or location, has the population been found to be homogeneous. Cells from progress zones and more proximal regions could all be resolved into several populations. The populations from progress zones at three different developmental stages were qualitatively similar but differed in the proportions of cells in each. The most striking differences in cell populations were those obtained from the most proximal region of the limb, closest to the flank, which represents the developmentally most advanced region.


Development ◽  
1981 ◽  
Vol 61 (1) ◽  
pp. 207-219
Author(s):  
Katrina J. Kirkwood ◽  
W. D. Billington

Mixed haemadsorption assays using antibody-coaled indicator sheep erythrocytes and mouse alloantisera revealed that major histocompatibility complex (H-2) antigens were expressed on cells of 24–72 h cultures of mid-gestation mouse embryonic skin, gut, lung, limb-bud and heart but not of embryonic gonad or kidney. The precise time of detection of H-2 antigen expression and the proportions of cells expressing these determinants depended on inbred strain, specific haplotype, tissue of origin and antiserum batch employed. In all tissues the proportion of cells expressing H-2 increased progressively from day 11–12 postcoitum onwards. The findings are discussed with respect to hypotheses concerning the possible role of major histocompatibility antigens in cellular recognition and interactions during embryogenesis.


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