ZFIN ID: ZDB-PERS-990210-19
Lawson, Nathan
Email: nathan.lawson@umassmed.edu
URL: http://lawsonlab.umassmed.edu
Affiliation: Lawson Lab
Address: Program in Gene Function and Expression University of Massachusetts Medical School Lazare Research Building, Room 617 364 Plantation Street Worcester, MA 01605 USA
Country: United States
Phone: Office: (508) 856-1177, Lab: (508) 856-2269 or 2605
Fax: (508) 856-5460


Peng, D., Ando, K., Hußmann, M., Gloger, M., Skoczylas, R., Mochizuki, N., Betsholtz, C., Fukuhara, S., Schulte-Merker, S., Lawson, N.D., Koltowska, K. (2022) Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells. eLIFE. 11:
Leonard, E.V., Figueroa, R.J., Bussmann, J., Lawson, N.D., Amigo, J.D., Siekmann, A.F. (2022) Regenerating vascular mural cells in zebrafish fin blood vessels are not derived from pre-existing ones and differentially require pdgfrb signalling for their development. Development (Cambridge, England). 149(7)
Shih, Y.H., Portman, D., Idrizi, F., Grosse, A., Lawson, N.D. (2021) Integrated molecular analysis identifies a conserved pericyte gene signature in zebrafish. Development (Cambridge, England). 148(23):
Shin, M., Lawson, N.D. (2021) Back and forth: History of and new insights on the vertebrate lymphatic valve. Development, growth & differentiation. 63(9):523-535
Ghanta, K.S., Chen, Z., Mir, A., Dokshin, G.A., Krishnamurthy, P.M., Yoon, Y., Gallant, J., Xu, P., Zhang, X.O., Ozturk, A.R., Shin, M., Idrizi, F., Liu, P., Gneid, H., Edraki, A., Lawson, N.D., Rivera-Pérez, J.A., Sontheimer, E., Watts, J.K., Mello, C.C. (2021) 5' modifications improve potency and efficacy of DNA donors for precision genome editing. eLIFE. 10:
Ando, K., Shih, Y.H., Ebarasi, L., Grosse, A., Portman, D., Chiba, A., Mattonet, K., Gerri, C., Stainier, D.Y.R., Mochizuki, N., Fukuhara, S., Betsholtz, C., Lawson, N.D. (2021) Conserved and context-dependent roles for pdgfrb signaling during zebrafish vascular mural cell development. Developmental Biology. 479:11-22
Peloggia, J., Münch, D., Meneses-Giles, P., Romero-Carvajal, A., Lush, M.E., Lawson, N.D., McClain, M., Pan, Y.A., Piotrowski, T. (2021) Adaptive cell invasion maintains lateral line organ homeostasis in response to environmental changes. Developmental Cell. 56(9):1296-1312.e7
Lawson, N.D., Li, R., Shin, M., Grosse, A., Yukselen, O., Stone, O.A., Kucukural, A., Zhu, L. (2020) An improved zebrafish transcriptome annotation for sensitive and comprehensive detection of cell type-specific genes. eLIFE. 9:
Shin, M., Nozaki, T., Idrizi, F., Isogai, S., Ogasawara, K., Ishida, K., Yuge, S., Roscoe, B., Wolfe, S.A., Fukuhara, S., Mochizuki, N., Deguchi, T., Lawson, N.D. (2019) Valves Are a Conserved Feature of the Zebrafish Lymphatic System. Developmental Cell. 51(3):374-386.e5
Whitesell, T.R., Chrystal, P.W., Ryu, J.R., Munsie, N., Grosse, A., French, C.R., Workentine, M.L., Li, R., Zhu, L.J., Waskiewicz, A., Lehmann, O.J., Lawson, N.D., Childs, S.J. (2019) foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish. Developmental Biology. 453(1):34-47
Lawson, N.D. (2019) On the Right Track: Meningeal Lymphatics Guide Angiogenesis during Tissue Repair in the Brain. Developmental Cell. 49:655-656
Liu, P., Luk, K., Shin, M., Idrizi, F., Kwok, S., Roscoe, B., Mintzer, E., Suresh, S., Morrison, K., Frazão, J.B., Bolukbasi, M.F., Ponnienselvan, K., Luban, J., Zhu, L.J., Lawson, N.D., Wolfe, S.A. (2019) Enhanced Cas12a editing in mammalian cells and zebrafish. Nucleic acids research. 47(8):4169-4180
Stainier, D.Y.R., Raz, E., Lawson, N.D., Ekker, S.C., Burdine, R.D., Eisen, J.S., Ingham, P.W., Schulte-Merker, S., Yelon, D., Weinstein, B.M., Mullins, M.C., Wilson, S.W., Ramakrishnan, L., Amacher, S.L., Neuhauss, S.C.F., Meng, A., Mochizuki, N., Panula, P., Moens, C.B. (2017) Guidelines for morpholino use in zebrafish. PLoS Genetics. 13:e1007000
Hasan, S.S., Tsaryk, R., Lange, M., Wisniewski, L., Moore, J.C., Lawson, N.D., Wojciechowska, K., Schnittler, H., Siekmann, A.F. (2017) Endothelial Notch signalling limits angiogenesis via control of artery formation. Nature cell biology. 19(8):928-940
Quillien, A., Abdalla, M., Yu, J., Ou, J., Zhu, L.J., Lawson, N.D. (2017) Robust Identification of Developmentally Active Endothelial Enhancers in Zebrafish Using FANS-Assisted ATAC-Seq. Cell Reports. 20:709-720
Lawson, N.D. (2017) A New Conserved Player in Lymphatic Morphogenesis. Circulation research. 120:1216-1218
Matsuoka, R.L., Marass, M., Avdesh, A., Helker, C.S., Maischein, H.M., Grosse, A.S., Kaur, H., Lawson, N.D., Herzog, W., Stainier, D.Y. (2016) Radial glia regulate vascular patterning around the developing spinal cord. eLIFE. 5
Shin, M., Beane, T., Quillien, A., Male, I., Zhu, L.J., Lawson, N.D. (2016) Vegfa signals through ERK to promote angiogenesis, but not artery differentiation. Development (Cambridge, England). 143(20):3796-3805
Shin, M., Male, I., Beane, T.J., Villefranc, J.A., Kok, F.O., Zhu, L.J., Lawson, N.D. (2016) Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors. Development (Cambridge, England). 143(20):3785-3795
Lawson, N.D. (2016) Reverse Genetics in Zebrafish: Mutants, Morphants, and Moving Forward. Trends in cell biology. 26(2):77-9
Shmukler, B.E., Lawson, N.D., Paw, B.H., Alper, S.L. (2016) Authors' response to "Comment on: 'Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia'". Haematologica. 101:e39
Hen, G., Nicenboim, J., Mayseless, O., Asaf, L., Shin, M., Busolin, G., Hofi, R., Almog, G., Tiso, N., Lawson, N.D., Yaniv, K. (2015) Venous-derived angioblasts generate organ-specific vessels during embryonic development. Development (Cambridge, England). 142(24):4266-78
Shmukler, B.E., Huston, N.C., Thon, J.N., Ni, C.W., Kourkoulis, G., Lawson, N.D., Paw, B.H., Alper, S.L. (2015) Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia. Haematologica. 100(12):e483-5
Nicenboim, J., Malkinson, G., Lupo, T., Asaf, L., Sela, Y., Mayseless, O., Gibbs-Bar, L., Senderovich, N., Hashimshony, T., Shin, M., Jerafi-Vider, A., Avraham-Davidi, I., Krupalnik, V., Hofi, R., Almog, G., Astin, J.W., Golani, O., Ben-Dor, S., Crosier, P.S., Herzog, W., Lawson, N.D., Hanna, J.H., Yanai, I., Yaniv, K. (2015) Lymphatic vessels arise from specialized angioblasts within a venous niche. Nature. 522(7554):56-61
Butko, E., Distel, M., Pouget, C., Weijts, B., Kobayashi, I., Ng, K., Mosimann, C., Poulain, F.E., McPherson, A., Ni, C.W., Stachura, D.L., Del Cid, N., Espín-Palazón, R., Lawson, N.D., Dorsky, R., Clements, W.K., Traver, D. (2015) Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. Development (Cambridge, England). 142:1050-61
Kok, F.O., Shin, M., Ni, C., Gupta, A., Grosse, A.S., van Impel, A., Kirchmaier, B.C., Peterson-Maduro, J., Kourkoulis, G., Male, I., DeSantis, D.F., Sheppard-Tindell, S., Ebarasi, L., Betsholtz, C., Schulte-Merker, S., Wolfe, S.A., Lawson, N.D. (2015) Reverse Genetic Screening Reveals Poor Correlation between Morpholino-Induced and Mutant Phenotypes in Zebrafish. Developmental Cell. 32(1):97-108
Carroll, K.J., Esain, V., Garnaas, M.K., Cortes, M., Dovey, M.C., Nissim, S., Frechette, G.M., Liu, S.Y., Kwan, W., Cutting, C.C., Harris, J.M., Gorelick, D.A., Halpern, M.E., Lawson, N.D., Goessling, W., North, T.E. (2014) Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Developmental Cell. 29:437-53
Quillien, A., Moore, J.C., Shin, M., Siekmann, A.F., Smith, T., Pan, L., Moens, C.B., Parsons, M.J., Lawson, N.D. (2014) Distinct Notch signaling outputs pattern the developing arterial system. Development (Cambridge, England). 141:1544-52
Kok, F.O., Gupta, A., Lawson, N.D., and Wolfe, S.A. (2014) Construction and application of site-specific artificial nucleases for targeted gene editing. Methods in molecular biology (Clifton, N.J.). 1101:267-303
Moore, J.C., Sheppard, S., Shestopalov, I.A., Chen, J.K., and Lawson, N. (2013) Post-transcriptional mechanisms contribute to Etv2 repression during vascular development. Developmental Biology. 384(1):128-40
Gupta, A., Hall, V.L., Kok, F.O., Shin, M., McNulty, J.C., Lawson, N.D., and Wolfe, S.A. (2013) Targeted Chromosomal Deletions and Inversions in Zebrafish. Genome research. 23(6):1008-17
Villefranc, J.A., Nicoli, S., Bentley, K., Jeltsch, M., Zarkada, G., Moore, J.C., Gerhardt, H., Alitalo, K., and Lawson, N.D. (2013) A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development (Cambridge, England). 140(7):1497-1506
Shin, J., Padmanabhan, A., de Groh, E.D., Lee, J.S., Haidar, S., Dahlberg, S., Guo, F., He, S., Wolman, M.A., Granato, M., Lawson, N.D., Wolfe, S.A., Kim, S.H., Solnica-Krezel, L., Kanki, J.P., Ligon, K.L., Epstein, J.A., and Look, A.T. (2012) Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development. Disease models & mechanisms. 5(6):881-894
Nicoli, S., Knyphausen, C.P., Zhu, L.J., Lakshmanan, A., and Lawson, N.D. (2012) miR-221 Is Required for Endothelial Tip Cell Behaviors during Vascular Development. Developmental Cell. 22(2):418-429
Cheung, I.D., Bagnat, M., Ma, T.P., Datta, A., Evason, K., Moore, J.C., Lawson, N.D., Mostov, K.E., Moens, C.B., and Stainier, D.Y. (2012) Regulation of intrahepatic biliary duct morphogenesis by Claudin 15-like b. Developmental Biology. 361(1):68-78
Delaval, B., Covassin, L., Lawson, N.D., and Doxsey, S. (2011) Centrin depletion causes cyst formation and other ciliopathy-related phenotypes in zebrafish. Cell cycle (Georgetown, Tex.). 10(22):3964-3972
Zhu, C., Smith, T., McNulty, J., Rayla, A.L., Lakshmanan, A., Siekmann, A.F., Buffardi, M., Meng, X., Shin, J., Padmanabhan, A., Cifuentes, D., Giraldez, A.J., Look, A.T., Epstein, J.A., Lawson, N.D., and Wolfe, S.A. (2011) Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development (Cambridge, England). 138(20):4555-4564
Aday, A.W., Zhu, L.J., Lakshmanan, A., Wang, J., and Lawson, N.D. (2011) Identification of cis regulatory features in the embryonic zebrafish genome through large-scale profiling of H3K4me1 and H3K4me3 binding sites. Developmental Biology. 357(2):450-62
Lawson, N.D., and Wolfe, S.A. (2011) Forward and reverse genetic approaches for the analysis of vertebrate development in the zebrafish. Developmental Cell. 21(1):48-64
Clements, W.K., Kim, A.D., Ong, K.G., Moore, J.C., Lawson, N.D., and Traver, D. (2011) A somitic Wnt16/Notch pathway specifies haematopoietic stem cells. Nature. 474(7350):220-224
Quillien, A., Blanco-Sanchez, B., Halluin, C., Moore, J.C., Lawson, N.D., Blader, P., and Cau, E. (2011) BMP signaling orchestrates photoreceptor specification in the zebrafish pineal gland in collaboration with Notch. Development (Cambridge, England). 138(11):2293-2302
Delaval, B., Bright, A., Lawson, N.D., and Doxsey, S. (2011) The cilia protein IFT88 is required for spindle orientation in mitosis. Nature cell biology. 13(4):461-468
Gupta, A., Meng, X., Zhu, L.J., Lawson, N.D., and Wolfe, S.A. (2011) Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases. Nucleic acids research. 39(1):381-392
Geudens, I., Herpers, R., Hermans, K., Segura, I., Ruiz de Almodovar, C., Bussmann, J., De Smet, F., Vandevelde, W., Hogan, B.M., Siekmann, A., Claes, F., Moore, J.C., Pistocchi, A.S., Loges, S., Mazzone, M., Mariggi, G., Bruyere, F., Cotelli, F., Kerjaschki, D., Noel, A., Foidart, J.M., Gerhardt, H., Ny, A., Langenberg, T., Lawson, N.D., Duckers, H.J., Schulte-Merker, S., Carmeliet, P., and Dewerchin, M. (2010) Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish. Arterioscler. Thromb. Vasc. Biol.. 30(9):1695-1702
Cifuentes, D., Xue, H., Taylor, D.W., Patnode, H., Mishima, Y., Cheloufim, S., Ma, E., Mane, S., Hannon, G.J., Lawson, N.D., Wolfe, S.A., and Giraldez, A.J. (2010) A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science (New York, N.Y.). 328(5986):1694-1698
Chapouton, P., Skupien, P., Hesl, B., Coolen, M., Moore, J.C., Madelaine, R., Kremmer, E., Faus-Kessler, T., Blader, P., Lawson, N.D., and Bally-Cuif, L. (2010) Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(23):7961-7974
Nicoli, S., Standley, C., Walker, P., Hurlstone, A., Fogarty, K.E., and Lawson, N.D. (2010) MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 464(7292):1196-1200
Lorent, K., Moore, J.C., Siekmann, A.F., Lawson, N., and Pack, M. (2010) Reiterative use of the notch signal during zebrafish intrahepatic biliary development. Developmental dynamics : an official publication of the American Association of Anatomists. 239(3):855-864
Padmanabhan, A., Lee, J.S., Ismat, F.A., Lu, M.M., Lawson, N.D., Kanki, J.P., Look, A.T., and Epstein, J.A. (2009) Cardiac and vascular functions of the zebrafish orthologues of the type I neurofibromatosis gene NFI. Proceedings of the National Academy of Sciences of the United States of America. 106(52):22305-22310
Parsons, M.J., Pisharath, H., Yusuff, S., Moore, J.C., Siekmann, A.F., Lawson, N., and Leach, S.D. (2009) Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mechanisms of Development. 126(10):898-912
Siekmann, A.F., Standley, C., Fogarty, K.E., Wolfe, S.A., and Lawson, N.D. (2009) Chemokine signaling guides regional patterning of the first embryonic artery. Genes & Development. 23(19):2272-2277
Covassin, L.D., Siekmann, A.F., Kacergis, M.C., Laver, E., Moore, J.C., Villefranc, J.A., Weinstein, B.M., and Lawson, N.D. (2009) A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Developmental Biology. 329(2):212-226
Meng, X., Noyes, M.B., Zhu, L.J., Lawson, N.D., and Wolfe, S.A. (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat. Biotechnol.. 26(6):695-701
Bussmann, J., Lawson, N., Zon, L., Schulte-Merker, S., and Zebrafish Nomenclature Committee. (2008) Zebrafish VEGF receptors: a guideline to nomenclature. PLoS Genetics. 4(5):e1000064
Hart, D.O., Raha, T., Lawson, N.D., and Green, M.R. (2007) Initiation of zebrafish haematopoiesis by the TATA-box-binding protein-related factor Trf3. Nature. 450(7172):1082-1085
Villefranc, J.A., Amigo, J., and Lawson, N.D. (2007) Gateway compatible vectors for analysis of gene function in the zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 236(11):3077-3087
Buchner, D.A., Su, F., Yamaoka, J.S., Kamei, M., Shavit, J.A., Barthel, L.K., McGee, B., Amigo, J.D., Kim, S., Hanosh, A.W., Jagadeeswaran, P., Goldman, D., Lawson, N.D., Raymond, P.A., Weinstein, B.M., Ginsburg, D., and Lyons, S.E. (2007) pak2a mutations cause cerebral hemorrhage in redhead zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 104(35):13996-140001
Pham, V.N., Lawson, N.D., Mugford, J.W., Dye, L., Castranova, D., Lo, B., and Weinstein, B.M. (2007) Combinatorial function of ETS transcription factors in the developing vasculature. Developmental Biology. 303(2):772-783
Siekmann, A.F., and Lawson, N.D. (2007) Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature. 445(7129):781-784
Covassin, L., Amigo, J.D., Suzuki, K., Teplyuk, V., Straubhaar, J., and Lawson, N.D. (2006) Global analysis of hematopoietic and vascular endothelial gene expression by tissue specific microarray profiling in zebrafish. Developmental Biology. 299(2):551-562
Alt, B., Elsalini, O.A., Schrumpf, P., Haufs, N., Lawson, N.D., Schwabe, G.C., Mundlos, S., Gruters, A., Krude, H., and Rohr, K.B. (2006) Arteries define the position of the thyroid gland during its developmental relocalisation. Development (Cambridge, England). 133(19):3797-3804
Covassin, L.D., Villefranc, J.A., Kacergis, M.C., Weinstein, B.M., and Lawson, N.D. (2006) Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 103(17):6554-6559
Hong, S.K., Haldin, C.E., Lawson, N.D., Weinstein, B.M., Dawid, I.B., and Hukriede, N.A. (2005) The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney. Proceedings of the National Academy of Sciences of the United States of America. 102(51):18473-18478
Crump, J.G., Maves, L., Lawson, N.D., Weinstein, B.M., and Kimmel, C.B. (2004) An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning. Development (Cambridge, England). 131(22):5703-5716
Huang, C., Lawson, N.D., Weinstein, B.M., and Johnson, S.L. (2003) reg6 is required for branching morphogenesis during blood vessel regeneration in zebrafish caudal fins. Developmental Biology. 264(1):263-274
Isogai, S., Lawson, N.D., Torrealday, S., Horiguchi, M., and Weinstein, B.M. (2003) Angiogenic network formation in the developing vertebrate trunk. Development (Cambridge, England). 130(21):5281-5290
Lawson, N.D., Mugford, J.W., Diamond, B.A., and Weinstein, B.M. (2003) phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development. Genes & Development. 17(11):1346-1351
Lawson, N.D. and Weinstein, B.M. (2002) Arteries and veins: making a difference with zebrafish. Nature reviews. Genetics. 3(9):674-682
Lawson, N.D. and Weinstein, B.M. (2002) In vivo imaging of embryonic vascular development using transgenic zebrafish. Developmental Biology. 248(2):307-318
Lawson, N.D., Vogel, A.M., and Weinstein, B.M. (2002) sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Developmental Cell. 3(1):127-136
Roman, B.L., Pham, V., Lawson, N.D., Kulik, M., Childs, S., Lekven, A.C., Garrity, D.M., Moon, R.T., Fishman, M.C., Lechleider, R.J., and Weinstein, B.M. (2002) Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. Development (Cambridge, England). 129(12):3009-3019
Lyons, S.E., Lawson, N.D., Lei, L., Bennett, P.E., Weinstein, B.M., and Liu, P.P. (2002) A nonsense mutation in zebrafish gata1 causes the bloodless phenotype in vlad tepes. Proceedings of the National Academy of Sciences of the United States of America. 99(8):5454-5459
Weinstein, B.M. and Lawson, N.D. (2002) Arteries, veins, Notch, and VEGF. Cold Spring Harbor symposia on quantitative biology. 67:155-162
Lawson, N.D., Scheer, N., Pham, V.N., Kim, C.-H., Chitnis, A.B., Campos-Ortega, J.A., and Weinstein, B.M. (2001) Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development (Cambridge, England). 128(19):3675-3683
Lyons, S.E., Lawson, N.D., Bennett, P.J., Weinstein, B.M., and Liu, P.P. (2000) Nonsense mutation in gata1 identified in the "bloodless" zebrafish vlad tepes. Blood. 96(11):2400

Lawson, N. D., Zain, M., Zibello, T., Picciotto, M. R., Nairn, A. C., and Berliner, N. (1999). A role for retinoic acid during neutrophil maturation: modulation of a calcium/calmodulin dependent kinase cascade. Exp Hematol, 27 (11), 1682-1690

Lawson, N. D. and Berliner, N. (1999) Neutrophil maturation and the role of retinoic acid. Exp Hematol 27 (9), 1355-1367.

Lawson, N. D., Krause, D. S., and Berliner, N. (1998). Normal neutrophil differentiation and secondary granule gene expression in the EML and MPRO cell lines. Exp Hematol 26, 1178-1185.

Lawson, N. D. and Berliner, N. (1998). Representational difference analysis of a committed myeloid progenitor cell line reveals evidence for bilineage potential. Proc Natl Acad Sci USA 95, 10129-10133

Lawson, N. D., Khanna-Gupta, A., and Berliner, N. (1998). Isolation and characterization of the cDNA for mouse neutrophil collagenase: Demonstration of shared negative regulatory pathways for neutrophil secondary granule protein gene expression. Blood 91(7), 2517-2524

Sigurdsson, F., Khanna-Gupta, A., Lawson, N., and Berliner, N. (1997). Control of late neutrophil-specific gene expression: insights into regulation of myeloid differentiation. Semin Hematol 34, 303-10.

Lawson, N. D., Stillman, E. A., Whitt, M. A., and Rose, J. K. (1995). Recombinant vesicular stomatitis viruses from DNA. Proc Natl Acad Sci USA 92, 4477-81