Malcolm Steinberg

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Malcolm Saul Steinberg (June 1, 1930 - February 7, 2012) was an American biologist [1] who proposed the differential adhesion hypothesis as a mechanism explaining cell sorting during embryogenesis and cancer. [2] [3] [4] [5]

Steinberg proposed that when cells form distinct tissues, specific cell-cell adhesion between cells from the same tissue can drive the separation. He further proposed that a difference in level of cell adhesion molecules expression between two cell types was sufficient to drive the separation. [6] He confirmed these predictions in a model system in which adhesion between cells of a cultured line of mouse cells was controlled by genetic expression levels of cadherin. [7]

Steinberg pioneered work in characterizing the physical properties of cells and tissues. He proposed that cell-cell adhesion drives tissue rounding up and, comparing tissues to liquids, he proposed that tissues have a surface tension. To measure tissue surface tension, he participated in building a compression device for rounded cell aggregates, [8] [9] and in sessile droplet experiments in which aggregates of cells were centrifuged at 37 degrees until their shapes reached equilibrium. [10] [11]

Later experiments led him to conclude that differential adhesion, and an adhesion gradient, guide the salamander pronephric duct to the cloaca during embryonic development. [12]

Steinberg completed his BS at Amherst College in 1952, his PhD in zoology at the University of Minnesota in 1956, was a professor of biology at Johns Hopkins University from 1958 to 1966, and transferred to Princeton University in 1966, becoming professor emeritus in 2005.

Related Research Articles

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<span class="mw-page-title-main">Adherens junction</span>

Adherens junctions are protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell or as spots of attachment to the extracellular matrix.

Compartments can be simply defined as separate, different, adjacent cell populations, which upon juxtaposition, create a lineage boundary. This boundary prevents cell movement from cells from different lineages across this barrier, restricting them to their compartment. Subdivisions are established by morphogen gradients and maintained by local cell-cell interactions, providing functional units with domains of different regulatory genes, which give rise to distinct fates. Compartment boundaries are found across species. In the hindbrain of vertebrate embryos, rhombomeres are compartments of common lineage outlined by expression of Hox genes. In invertebrates, the wing imaginal disc of Drosophila provides an excellent model for the study of compartments. Although other tissues, such as the abdomen, and even other imaginal discs are compartmentalized, much of our understanding of key concepts and molecular mechanisms involved in compartment boundaries has been derived from experimentation in the wing disc of the fruit fly.

Differential adhesion hypothesis (DAH) is a hypothesis that explains cellular movement during morphogenesis with thermodynamic principles. In DAH tissues are treated as liquids consisting of mobile cells whose varying degrees of surface adhesion cause them to reorganize spontaneously to minimize their interfacial free energy. Put another way, according to DAH, cells move to be near other cells of similar adhesive strength in order to maximize the bonding strength between cells and produce a more thermodynamically stable structure. In this way the movement of cells during tissue formation, according to DAH, parodies the behavior of a mixture of liquids. Although originally motivated by the problem of understanding cell sorting behavior in vertebrate embryos, DAH has subsequently been applied to explain several other morphogenic phenomena.

α-Catenin Primary protein link between cadherins and the actin cytoskeleton

α-Catenin (alpha-catenin) functions as the primary protein link between cadherins and the actin cytoskeleton. It has been reported that the actin binding proteins vinculin and α-actinin can bind to alpha-catenin. It has been suggested that alpha-catenin does not bind with high affinity to both actin filaments and the E-cadherin-beta-catenin complex at the same time. It has been observed that when α-catenin is not in a molecular complex with β-catenin, it dimerizes and functions to regulate actin filament assembly, possibly by competing with Arp2/3 protein. α-Catenin exhibits significant protein dynamics. However, a protein complex including a cadherin, actin, β-catenin and α-catenin has not been isolated.

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<span class="mw-page-title-main">CDH6</span> Protein-coding gene in the species Homo sapiens

Cadherin-6 is a protein that in humans is encoded by the CDH6 gene.

<span class="mw-page-title-main">CDH15</span> Protein-coding gene in the species Homo sapiens

Cadherin-15 is a protein that in humans is encoded by the CDH15 gene.

<span class="mw-page-title-main">PCDHB16</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-16 is a protein that in humans is encoded by the PCDHB16 gene.

<span class="mw-page-title-main">CDH12</span> Protein-coding gene in the species Homo sapiens

Cadherin-12 is a protein that in humans is encoded by the CDH12 gene.

<span class="mw-page-title-main">PCDHB13</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-13 is a protein that in humans is encoded by the PCDHB13 gene.

<span class="mw-page-title-main">PCDHB14</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-14 is a protein that in humans is encoded by the PCDHB14 gene.

<span class="mw-page-title-main">PCDHB11</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-11 is a protein that in humans is encoded by the PCDHB11 gene.

<span class="mw-page-title-main">PCDHB2</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-2 is a protein that in humans is encoded by the PCDHB2 gene.

<span class="mw-page-title-main">PCDH7</span> Protein-coding gene in the species Homo sapiens

Protocadherin-7 is a protein that in humans is encoded by the PCDH7 gene.

<span class="mw-page-title-main">PCDHB9</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-9 is a protein that in humans is encoded by the PCDHB9 gene.

<span class="mw-page-title-main">PCDHB7</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-7 is a protein that in humans is encoded by the PCDHB7 gene.

<span class="mw-page-title-main">PCDHB4</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-4 is a protein that in humans is encoded by the PCDHB4 gene.

<span class="mw-page-title-main">PCDHB12</span> Protein-coding gene in humans

Protocadherin beta-12 is a protein that in humans is encoded by the PCDHB12 gene.

<span class="mw-page-title-main">PCDHB3</span> Protein-coding gene in the species Homo sapiens

Protocadherin beta-3 is a protein that in humans is encoded by the PCDHB3 gene.

References

  1. Obituary
  2. Steinberg, Malcolm S. (1962). "On the mechanism of tissue reconstruction by dissociated cells, I. Population kinetics, differential adhesiveness, and the absence of directed migration". Proc Natl Acad Sci USA. 48 (9): 1577–1582. Bibcode:1962PNAS...48.1577S. doi: 10.1073/pnas.48.9.1577 . PMC   221002 . PMID   13916689.
  3. Steinberg, Malcolm S. (1962). "Mechanism of tissue reconstruction by dissociated cells. II. Time-course of events". Science. 137 (3532): 762–3. Bibcode:1962Sci...137..762S. doi:10.1126/science.137.3532.762. PMID   13916688. S2CID   29591598 . Retrieved May 19, 2021.
  4. Steinberg, Malcolm S. (1963). "Reconstruction of tissues by dissociated cells. Some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation". Science. 141 (3579): 401–8. doi:10.1126/science.141.3579.401. PMID   13983728 . Retrieved May 19, 2021.
  5. Steinberg, Malcolm S. (1970). "Does differential adhesion govern self-assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells". J Exp Zool. 173 (4): 395–433. Bibcode:1970JEZ...173..395S. doi:10.1002/jez.1401730406. PMID   5429514 . Retrieved May 19, 2021.
  6. Steinberg, Malcolm S. (1975). "Adhesion-guided multicellular assembly: a commentary upon the postulates, real and imagined, of the differential adhesion hypothesis, with special attention to computer simulations of cell sorting". J Theor Biol. 55 (2): 431–43. Bibcode:1975JThBi..55..431S. doi:10.1016/s0022-5193(75)80091-9. PMID   1207170 . Retrieved May 19, 2021.
  7. Steinberg, Malcolm S.; Takeichi, Masatoshi (1994). "Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression". Proc Natl Acad Sci USA. 91 (1): 206–9. Bibcode:1994PNAS...91..206S. doi: 10.1073/pnas.91.1.206 . PMC   42915 . PMID   8278366.
  8. Foty, Ramsey A.; Pfleger, Cathie M.; Forgacs, Gabor; Steinberg, Malcolm S. (1996). "Surface tensions of embryonic tissues predict their mutual envelopment behavior". Development. 122 (5): 1611–20. doi:10.1242/dev.122.5.1611. PMID   8625847 . Retrieved May 19, 2021.
  9. Davis, Grayson S.; Phillips, Herbert M.; Steinberg, Malcolm S. (1997). "Germ-layer surface tensions and "tissue affinities" in Rana pipiens gastrulae: quantitative measurements". Dev Biol. 192 (2): 630–44. doi: 10.1006/dbio.1997.8741 . PMID   9441694.
  10. Phillips, Herbert M.; Steinberg, Malcolm S. (1969). "Equilibrium measurements of embryonic chick cell adhesiveness. I. Shape equilibrium in centrifugal fields". Proc Natl Acad Sci USA. 64 (1): 1212–7. Bibcode:1969PNAS...64..121P. doi: 10.1073/pnas.64.1.121 . PMC   286135 . PMID   5262993.
  11. Phillips, Herbert M.; Steinberg, Malcolm S. (1978). "Embryonic tissues as elasticoviscous liquids. I. Rapid and slow shape changes in centrifuged cell aggregates". J Cell Sci. 30: 1–20. doi:10.1242/jcs.30.1.1. PMID   649680 . Retrieved May 19, 2021.
  12. Steinberg, Malcolm S.; Poole, Thomas J. (1981). "Strategies for specifying form and pattern: adhesion-guided multicellular assembly". Philos Trans R Soc Lond B Biol Sci. 295 (1078): 451–60. Bibcode:1981RSPTB.295..451S. doi:10.1098/rstb.1981.0153. PMID   6117905 . Retrieved May 19, 2021.