Avoiding aneuploidy

1
Avoiding aneuploidy CAMPBELL, M. S. and CORBSKY, C. J. (1995) Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope antibody delays the onset of anaphase 1. Cell Bid. 129, 1195-I 204 During meiosis and mitosis, a single misplaced chromosome can block or delay chromosome separation in anaphase. This is a result of a meta- phase checkpoint that functions in a number of different organisms and, in this way, cells avoid becoming aneuploid. Campbell and Corbsky provide evidence indicating that a phospho- epitope at the chromosomal kineto- chores plays a major role in this checkpoint. When viewed by im- munofluorescence microscopy, the monoclonal antibody 3F3/2, which recognizes this epitope, intensely stained kinetochores of chromosomes that were not attached to the mitotic spindle, and it was found that one member of each sister kinetochore pair was always brighter than its partner. Chromosomes moving to- wards the metaphase plate showed a reduced signal, whereas those aligned at the metaphase plate did not stain at all. The normal dephosphorylation of the 3F3/2 phosphoepitope could be inhibited by microinjection of the antibody that recognizes 3F3/2. This caused a delay in the onset of anaphase as well as the disappearance of the asymmetric expression of the phosphoepitope on the kinetochore pairs. However, movement of chro- mosomes to the metaphase plate was unaffected, suggesting that the epi- tope does not regulate the mechanics of chromosome movement. Any drug-induced perturbation of micro- tubules in metaphase cells resulted in the rapid reappearance of the 3F3/2 phosphoepitope, hinting that the epi- tope may be part of a sensor that determines whether kinetochores are attached to spindle microtubules. This work provides further import- ant evidence that the 3F3/2 epitope is part of a checkpoint pathway regu- lating the metaphase-to-anaphase transition. Homing, sweet homing MASTELLER, E. L. et al. (1995) Chicken B cells undergo discrete developmental changes in surface carbohydrate structure that appear to play a role in directing lymphocyte migration during embryogenesis Development 121 ,I 657-1667 SONG, J. and ZIPSER, B. (1995) Targeting of neuronal subsets mediated by their sequentially expressed carbohydrate markers Neuron 14, 537-547 Although there are intriguing descriptions of temporal and spatial restrictions in the expression of cell surface carbohydrates, their developmental significance has remained obscure. Recently, functional correlates of restricted carbohydrate expression have been described supporting the hypothesis that the specificity of embryonic cell-cell interactions depends on the array of cell surface carbohydrates and their complementary receptors expressed during development. Progenitors of B cells in chick embryos find their way from haematopoietic tissue to the bursa of Fabricius where they undergo clonal expansion and differentiation. Heterochronic transplantations demonstrate that young progenitor cells can home to a bursa of any age but older progenitor cells fail to home correctly. Here, Masteller et al. report that B cell progenitors express a carbohydrate epitope, sialyl Lewis x, while they are homing- competent. As progenitor populations become less able to home, expression of sialyl Lewis x decreases. Perturbations of sialyl Lewis x structures block adhesion of a B-progenitor-like cell line to bursal tissue. Therefore, homing of avian B progenitor cells to the bursa of Fabricius resembles selectin- mediated homing of leukocytes in mammals and suggests that a protein receptor recognizing a carbohydrate epitope remains to be found in bursal tissue. In the embryonic nervous system, pathfinding, or the ability of neural pro- cesses to find and associate with appropriate partners, can be considered the equivalent of homing. Recently, Song and Zipser demonstrated the regu- lated expression of carbohydrate epitopes on subsets of sensory axons in the leech embryo. Disruption of one carbohydrate epitope blocks the axonal defasciculation (unbundling) normally seen during early growth of sensory fibres into the central nervous system. Disruption of epitopes expressed later in development generates axonal defasciculation and hence interferes with targeting. These specific and antagonistic perturbations suggest that carbohydrates serve as ligands. Identification of protein receptors that mediate pathfinding through recognition of carbohydrate structures might reveal the extent to which embryonic neurons and lymphocyte progenitors act alike. HEADLINES The HEADLINES section of trends in CELL BIOLOGY is intended to draw attention to a selection of research papers of importance to cell biology that have been published in the past few months. Headlines are contributed regularly by a panel of research scientists appointed by the Editor. Please contact the trends in CELL BIOLOGY editorial team if you are interested in writing for the Headlines section. TRENDS IN CELL BIOLOGY VOL. 5 SEPTEMBER 1995 This month’s headlines were contributed by lsabelle Delumeau, Donald Cullberg, Peter van der Sluijs, Debbie Sweet, Michael Tiemeyer and Sylvie Tournier. 347

Transcript of Avoiding aneuploidy

Avoiding aneuploidy

CAMPBELL, M. S. and CORBSKY, C. J. (1995)

Microinjection of mitotic cells with the 3F3/2 anti-phosphoepitope

antibody delays the onset of anaphase

1. Cell Bid. 129, 1195-I 204

During meiosis and mitosis, a single misplaced chromosome can block or delay chromosome separation in anaphase. This is a result of a meta- phase checkpoint that functions in a number of different organisms and, in this way, cells avoid becoming aneuploid.

Campbell and Corbsky provide evidence indicating that a phospho- epitope at the chromosomal kineto- chores plays a major role in this checkpoint. When viewed by im- munofluorescence microscopy, the monoclonal antibody 3F3/2, which recognizes this epitope, intensely stained kinetochores of chromosomes that were not attached to the mitotic spindle, and it was found that one member of each sister kinetochore pair was always brighter than its partner. Chromosomes moving to- wards the metaphase plate showed a reduced signal, whereas those aligned at the metaphase plate did not stain at all.

The normal dephosphorylation of the 3F3/2 phosphoepitope could be inhibited by microinjection of the antibody that recognizes 3F3/2. This caused a delay in the onset of anaphase as well as the disappearance of the asymmetric expression of the phosphoepitope on the kinetochore pairs. However, movement of chro- mosomes to the metaphase plate was unaffected, suggesting that the epi- tope does not regulate the mechanics of chromosome movement. Any drug-induced perturbation of micro- tubules in metaphase cells resulted in the rapid reappearance of the 3F3/2 phosphoepitope, hinting that the epi- tope may be part of a sensor that determines whether kinetochores are attached to spindle microtubules.

This work provides further import- ant evidence that the 3F3/2 epitope is part of a checkpoint pathway regu- lating the metaphase-to-anaphase transition.

Homing, sweet homing

MASTELLER, E. L. et al. (1995) Chicken B cells undergo discrete developmental changes in surface

carbohydrate structure that appear to play a role in directing lymphocyte migration during embryogenesis

Development 121 ,I 657-1667

SONG, J. and ZIPSER, B. (1995) Targeting of neuronal subsets mediated by their sequentially expressed

carbohydrate markers Neuron 14, 537-547

Although there are intriguing descriptions of temporal and spatial restrictions in the expression of cell surface carbohydrates, their developmental significance has remained obscure. Recently, functional correlates of restricted carbohydrate expression have been described supporting the hypothesis that the specificity of embryonic cell-cell interactions depends on the array of cell surface carbohydrates and their complementary receptors expressed during development.

Progenitors of B cells in chick embryos find their way from haematopoietic tissue to the bursa of Fabricius where they undergo clonal expansion and differentiation. Heterochronic transplantations demonstrate that young progenitor cells can home to a bursa of any age but older progenitor cells fail to home correctly. Here, Masteller et al. report that B cell progenitors express a carbohydrate epitope, sialyl Lewis x, while they are homing- competent. As progenitor populations become less able to home, expression of sialyl Lewis x decreases. Perturbations of sialyl Lewis x structures block adhesion of a B-progenitor-like cell line to bursal tissue. Therefore, homing of avian B progenitor cells to the bursa of Fabricius resembles selectin- mediated homing of leukocytes in mammals and suggests that a protein receptor recognizing a carbohydrate epitope remains to be found in bursal tissue.

In the embryonic nervous system, pathfinding, or the ability of neural pro- cesses to find and associate with appropriate partners, can be considered the equivalent of homing. Recently, Song and Zipser demonstrated the regu- lated expression of carbohydrate epitopes on subsets of sensory axons in the leech embryo. Disruption of one carbohydrate epitope blocks the axonal defasciculation (unbundling) normally seen during early growth of sensory fibres into the central nervous system. Disruption of epitopes expressed later in development generates axonal defasciculation and hence interferes with targeting. These specific and antagonistic perturbations suggest that carbohydrates serve as ligands. Identification of protein receptors that mediate pathfinding through recognition of carbohydrate structures might reveal the extent to which embryonic neurons and lymphocyte progenitors act alike.

HEADLINES The HEADLINES section of trends in CELL BIOLOGY is

intended to draw attention to a selection of research papers of importance to cell biology that have been published in the

past few months. Headlines are contributed regularly by a panel of research scientists appointed by the Editor.

Please contact the trends in CELL BIOLOGY editorial team if you are interested in writing for the Headlines section.

TRENDS IN CELL BIOLOGY VOL. 5 SEPTEMBER 1995

This month’s headlines were contributed by lsabelle Delumeau, Donald Cullberg, Peter van der Sluijs, Debbie Sweet, Michael Tiemeyer and Sylvie Tournier.

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