Over many years evidence has accumulated that plants and animals can regulate growth with reference to overall size rather than cell number. Thus, organs and organisms grow until they reach their characteristic size and shape and then they stop - they can even compensate for experimental manipulations that change, over several fold, cell number or average cell size. If the cell size is altered, the organism responds with a change in cell number and vice versa. We look at the Drosophila wing in more detail: here, both extracellular and intracellular regulators have been identified that link cell growth, division and cell survival to final organ size. We discuss a hypothesis that the local steepness of a morphogen gradient is a measure of length in one axis, a measure that is used to determine whether there will be net growth or not.
REFERENCES
Blair
S. S.
(1995
) Compartments and appendage development in Drosophila.
BioEssays
17
, 299
–309
Blair
S. S.
, Ralston
A.
(1997
) Smoothened-mediated Hedgehog signalling is required for the maintenance of the anterior-posterior lineage restriction in the developing wing of Drosophila.
Development
124
, 4053
–4063
Böhni
R.
, Riesgo-Escovar
J.
, Oldham
S.
, Brogiolo
W.
, Stocker
H.
, Andruss
B. F.
, Beckingham
K.
, Hafen
E.
(1999
) Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4.
Cell
97
, 865
–875
Britton
J. S.
, Edgar
B. A.
(1998
) Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms.
Development
125
, 2149
–2158
Bryant
P. J.
, Levinson
P.
(1985
) Intrinsic growth control in the imaginal primordia of Drosophila, and the autonomous action of a lethal mutation causing overgrowth.
Dev. Biol
107
, 355
–363
Bryant
S. V.
, French
V.
, Bryant
P. J.
(1981
) Distal regeneration and symmetry.
Science
212
, 993
–1002
Burke
R.
, Basler
K.
(1996
) Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing.
Development
122
, 2261
–2269
Busturia
A.
, Lawrence
P. A.
(1994
) Regulation of cell number in Drosophila.
Nature
370
, 561
–563
Cadigan
K. M.
, Fish
M. P.
, Rulifson
E. J.
, Nusse
R.
(1998
) Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing.
Cell
93
, 767
–777
Campbell
G.
, Tomlinson
A.
(1999
) Transducing the Dpp morphogen gradient in the wing of Drosoophila: Regulation of Dpp targets by brinker.
Cell,
96
, 553
–562
Capdevilla
J.
, Guerrero
I.
(1994
) Targeted expression of the signalling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings.
EMBO J
13
, 4459
–4468
Cavodeassi
F.
, Diez del Corral
R.
, Campuzano
S.
, Dominguez
M.
(1999
) Compartments and organising boundaries in the Drosophila eye: the role of the homeodomain Iroquois proteins.
Development
126
, 4933
–4942
Chen
C.
, Jack
J.
, Garofalo
R. S.
(1996
) The Drosophila insulin receptor is required for normal growth.
Endocrinology
137
, 846
–856
Conlon
I.
, Raff
M.
(1999
) Size control in animal development.
Cell
96
, 235
–244
Couso
J. P.
, Bishop
S. A.
, Martinez Arias
A.
(1994
) The wingless signalling pathway and the patterning of the wing margin in Drosophila.
Development
120
, 621
–636
de Celis
J. F.
, Barrio
R.
, Kafatos
F. C.
(1996
) A gene complex acting downstream of dpp in Drosophila wing morphogenesis.
Nature
381
, 421
–424
Diaz-Benjumea
F. J.
, Cohen
S. M.
(1995
) Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing.
Development
121
, 4215
–4225
Doerner
P.
, Jørgensen
J.-E.
, You
R.
, Steppuhn
J.
, Lamb
C.
(1996
) Control of root growth and development by cyclin expression.
Nature
380
, 520
–523
Edgar
B. A.
, Lehner
C. F.
(1996
) Developmental control of cell cycle regulators: a fly's perspective.
Science
274
, 1646
–1652
Fero
M. L.
, Rivkin
M.
, Tasch
M.
, Porter
P.
, Carow
E. C.
, Firpo
E.
, Polyak
K.
, Tsai
L.-H.
, Broudy
V.
, Perlmutter
R. M.
, Kaushansky
K.
, Roberts
J. M.
(1996
) A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kip1-deficient mice.
Cell
85
, 733
–744
Frankhauser
G.
(1945
) The effects of changes in chromosome number on amphibian development.
Quart. Rev. Biol
20
, 20
–78
French
V.
, Bryant
P. J.
, Bryant
S. V.
(1976
) Pattern regulation in epimorphic fields.
Science
193
, 969
–981
Garcia-Bellido
A.
, Merriam
J. R.
(1971
) , Parameters of the wing imaginal disc development of Drosophila melanogaster.
Dev. Biol
24
, 61
–87
Garcia-Bellido
A.
, Lawrence
P. A.
, Morata
G.
(1979
) Compartments in animal development.
Scient. Am
241
, 102
–110
Garg
U. C.
, Hassid
A.
(1989
) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.
J. Clin. Invest
83
, 1774
–1777
Gonzalez-Gaitan
M.
, Capdevila
M. P.
, García-Bellido
A.
(1994
) Cell proliferation patterns in the wing imaginal disc of Drosophila.
Mech. Dev
40
, 183
–200
Hartenstein
V.
, Posakony
J. W.
(1989
) Development of adult sensilla on the wing and notum of Drosophila melanogaster.
Development
107
, 389
–405
Hemerly
A.
, de Almeida Engler
J.
, Bergounioux
C.
, Van Montagu
M.
, Engler
G.
, Inze
D.
, Ferreira
P.
(1995
) Dominant negative mutants of the Cdc2 kinase uncouple cell division from iterative plant development.
EMBO J
14
, 3925
–3936
Henery
C. C.
, Bard
J. B. L.
, Kaufman
M. H.
(1992
) Tetraploidy in mice, embryonic cell number, and the grain of the developmental map.
Dev. Biol
152
, 233
–241
Ito
N.
, Rubin
G. M.
(1999
) gigas, a Drosophila homolog of Tuberous Sclerosis Gene Product-2, regulates the cell cycle.
Cell
96
, 529
–539
Jazwinska
A.
, Kirov
N.
, Wieschaus
E.
, Roth
S.
, Rushlow
C.
(1999
) The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation.
Cell,
96
, 563
–573
Johnston
L. A.
, Edgar
B. A.
(1998
) Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing.
Nature
394
, 82
–84
Johnston
L. A.
, Prober
D. A.
, Edgar
B. A.
, Eisenman
R. N.
, Gallant
P.
(1999
) Drosophilamyc regulates cellular growth during development.
Cell
98
, 779
–790
Jones
A. M.
, Im
K.-H.
, Savka
M. A.
, Wu
M.-J.
, DeWitt
N. G.
, Shillito
R.
, Binns
A. N.
(1998
) Auxin-dependent cell expansion mediated by overexpressed Auxin-Binding Protein 1.
Science
282
, 1114
–1117
Jursnich
V. A.
, Fraser
S. E.
, Held
L. I.
Jr., Ryerse
J.
, Bryant
P. J.
(1990
) Defective gap-junctional communication associated with imaginal disc overgrowth and degeneration caused by mutations of the dco gene in Drosophila.
Dev. Biol
140
, 413
–429
Kaplan
D. R.
, Hagemann
W.
(1991
) The relationship of cell and organism in vascular plants.
Bioscience
41
, 693
–703
Kawamura
K.
, Shibata
T.
, Saget
O.
, Peel
D.
, Bryant
P. J.
(1999
) A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells.
Development
126
, 211
–219
Kiyokawa
H.
, Kineman
R. D.
, Manova-Todorava
K. O.
, Soares
V. C.
, Hoffman
E. S.
, Ono
M.
, Khanam
D.
, Hayday
A. C.
, Frohman
L. A.
, Koff
A.
(1996
) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1.
Cell
85
, 721
–731
Kuzin
B.
, Roberts
I.
, Peunova
N.
, Enikolopov
G.
(1996
) Nitric oxide regulates cell proliferation during Drosophila development.
Cell
87
, 639
–649
Kwon
S. K.
, Stuehr
D. J.
, Nathan
C. F.
(1991
) Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide.
J. Exp. Med
174
, 761
–767
Lawrence
P. A.
, Struhl
G.
(1996
) Morphogens, compartments and pattern: lessons from Drosophila?.
Cell
85
, 951
–961
Lawrence
P. A.
(1966
) Gradients in the insect segment, the orientation of hairs in the milkweed bug.
J. exp. Biol
44
, 607
–620
Lawrence
P. A.
, Morata
G.
(1976
) Compartments in the wing of Drosophila, a study of the engrailed gene.
Dev. Biol.,
50
, 321
–337
Lawrence
P. A.
, Casal
J.
, Struhl
G.
(1999
) The hedgehog morphogen and gradients of cell affinity in the abdomen of Drosophila.
Development
126
, 2441
–2449
Lawrence
P. A.
, Sanson
B.
, Vincent
J. P.
(1996
) Compartments, wingless and engrailed: patterning the ventral epidermis of Drosophila embryos.
Development
122
, 4095
–4103
Lecuit
T.
, Brook
W. J.
, Ng
M.
, Calleja
M.
, Sun
H.
, Cohen
S. M.
(1996
) Two distinct mechanisms for long-range patterning by decapentaplegic in the Drosophila wing.
Nature
381
, 387
–393
Lecuit
T.
, Cohen
S. M.
(1998
) Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc.
Development
125
, 4901
–4907
Leevers
S. J.
, Weinkove
D.
, MacDougall
L. K.
, Hafen
E.
, Waterfield
M. D.
(1996
) The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth.
EMBO J
15
, 6584
–6594
Lepoivre
M.
, Chenais
B.
, Yapo
A.
, Lemaire
G.
, Thelander
L.
, Tenu
J. P.
(1990
) Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells.
J. Biol. Chem
265
, 14143
–14149
Li
Q. J.
, Pazdera
T. M.
, Minden
J. S.
(1999
) Drosophila embryonic pattern repair: how embryos respond to cyclin E-induced ectopic division.
Development
126
, 2299
–2307
Meneses
P.
, De Los Angeles Ortiz
M.
(1975
) A protein extract from Drosophila melanogaster with insulin-like activity.
Comp. Biochem. Physiol. A
51
, 483
–485
Milán
M.
, Cohen
S. M.
(2000
) Subdividing cell populations in the developing limbs of Drosophila: Do wing veins and leg segments define units of growth control?.
Dev. Biol
217
, 1
–9
Milán
M.
, Campuzano
S.
, García-Bellido
A.
(1996
) Cell cycling and patterned cell proliferation in the wing primordium of Drosophila.
Proc. Natl. Acad. Sci. USA
93
, 640
–645
Minami
M.
, Kinoshita
N.
, Kamoshida
Y.
, Tanimoto
H.
, Tabata
T.
(1999
) brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes.
Nature,
398
, 242
–246
Mizukami
Y.
, Fischer
R. L.
(2000
) Plant organ size control: AINTEGUMENTA regulates growth and cell numbers during organogenesis.
Proc. Natl. Acad. Sci. USA
97
, 942
–947
Montagne
J.
, Stewart
M. J.
, Stocker
H.
, Hafen
E.
, Kozma
S. C.
, Thomas
G.
(1999
) Drosophila S6 kinase. A regulator of cell size.
Science
285
, 2126
–2129
Morata
G.
, Ripoll
P.
(1975
) Minutes: mutants of Drosophila autonomously affecting cell division rate.
Dev. Biol
427
, 211
–221
Nagaraj
R.
, Pickup
A. T.
, Howes
R.
, Moses
K.
, Freeman
M.
, Banerjee
U.
(1999
) Role of the EGF receptor pathway in growth and patterning of the Drosophila wing through the regulation of vestigial.
Development
126
, 975
–985
Nakayama
K.
, Ishida
N.
, Shirane
M.
, Inomata
A.
, Inoue
T.
, Shishido
N.
, Horii
I.
, Loh
D. Y.
, Nakayama
K.
(1996
) Mice lacking p27Kip1display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.
Cell
85
, 707
–720
Namba
R.
, Pazdera
T. M.
, Cerrone
R. L.
, Minden
J. S.
(1997
) Drosophila embryonic pattern repair: how embryos respond to bicoid dosage alteration.
Development
124
, 1393
–1403
Nellen
D.
, Burke
R.
, Struhl
G.
, Basler
K.
(1996
) Direct and long-range action of a Dpp morphogen gradient.
Cell
85
, 357
–368
Neufeld
T. P.
, Edgar
B. A.
(1998
) Connections between growth and the cell cycle.
Curr. Opin. Cell Biology
10
, 784
–790
Neufeld
T. P.
, de la Cruz
A. F. A.
, Johnston
L. A.
, Edgar
B. A.
(1998
) Coordination of growth and cell division in the Drosophila wing.
Cell
93
, 1183
–1193
Newman
C. J.
, Cohen
S. M.
(1997
) Morphogens and pattern formation.
Bioessays
19
, 721
–729
Ng
M.
, Diaz-Benjumea
F. J.
, Vincent
J. P.
, Wu
J.
, Cohen
S. M.
(1996
) Specification of the wing by localized expression of wingless protein.
Nature
381
, 316
–318
Nijhout
H. F.
, Emlen
D. J.
(1998
) Competition among body parts in the development and evolution of insect morphology.
Proc. Natl. Acad. Sci. USA
95
, 3685
–3689
O'Brochta
D. A.
, Bryant
P. J. A.
(1985
) A zone of non-proliferating cells at a lineage restriction boundary in Drosophila.
Nature
313
, 138
–141
Parent
C. A.
, Devreotes
P. N.
(1999
) A cell's sense of direction.
Science
284
, 765
–770
Parent
C. A.
, Blacklock
B. J.
, Froehlich
W. M.
, Murphy
D. B.
, Devreotes
P. N.
(1998
) G protein signalling events are activated at the leading edge of chemotactic cells.
Cell
95
, 81
–91
Peifer
M.
, Rauskolb
C.
, Williams
M.
, Riggleman
B.
, Wieschaus
E.
(1991
) The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation.
Development
111
, 1029
–1043
Phillips
R. G.
, Whittle
J. R.
(1993
) wingless expression mediates determination of peripheral nervous system elements in the late stages of Drosophila wing disc development.
Development
118
, 427
–438
Poethig
R. S.
(1987
) Clonal analysis of cell lineage patterns in plant development.
Am. J. Bot
74
, 581
–594
Rodriguez
I.
, Basler
K.
(1997
) Control of compartmental affinity boundaries by Hedgehog.
Nature
389
, 614
–618
Santamaria
P.
(1983
) Analysis of haploid mosaics in Drosophila.
Dev. Biol
96
, 285
–295
Satina
S.
, Blakeslee
A. F.
(1941
) Periclinal chimeras in Datura stramonium in relation to the development of the leaf and flower.
Am. J. Bot
28
, 862
–871
Satina
S.
, Blakeslee
A. F.
, Avery
A. G.
(1940
) Demonstration of the three germ layers in the shoot apex of Datura by means of induced polyploidy in periclinal chimeras.
Am. J. Bot
27
, 895
–905
Seecof
R. L.
, Dewhurst
S.
(1974
) Insulin is a Drosophila hormone and acts to enhance the differentiation of embryonic Drosophila cells.
Cell Differ
3
, 63
–70
Serrano
N.
, O'Farrell
P. H.
(1997
) Limb morphogenesis: connections between patterning and growth.
Curr. Biol
7
, 186
–.Servant
G.
, Weiner
O. D.
, Herzmark
P.
, Balla
T.
, Sedat
J. W.
, Bourne
H. R.
(2000
) Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis.
Science
287
, 1037
–1040
Sharma
R. P.
, Chopra
V. L.
(1976
) Effect of the wingless (wg1) mutation on wing and haltere development in Drosophil a melanogaster.
Dev. Biol
48
, 461
–465
Simpson
P.
(1976
) Analysis of the compartments of the wing of Drosophila melanogaster. Mosaic for a temperature-sensitive mutation that reduces mitotic rate.
Dev. Biol
54
, 100
–115
Simpson
P.
(1979
) , Parameters of cell competition in the compartments of the wing disc of Drosophila.
Dev. Biol
69
, 182
–193
Simpson
P.
, Morata
G.
(1981
) Differential mitotic rates and patterns of growth in compartments in the Drosophila wing.
Dev. Biol
85
, 299
–308
Smith
L. G.
, Hake
S.
, Sylvester
A. W.
(1996
) The tangled-1 mutation alters cell division orientations throughout maize leaf development without altering leaf shape.
Development
122
, 481
–489
Sobels
F. H.
(1952
) Genetics and morphology of the genotype ‘asymmetric’ with special reference to its ‘abnormal abdomen’ character.
Genetica,
26
, 117
–279
Spencer
F. A.
, Hoffman
F. M.
, Gelbart
W. M.
(1982
) Decapentaplegic: a gene complex affecting morphogenesis in Drosophilamelanogaster.
Cell
28
, 451
–461
Steinberg
M. S.
(1963
) Reconstruction of tissues by dissociated cells.
Science
141
, 401
–408
Stern
D. L.
, Emlen
D. J.
(1999
) The developmental basis for allometry in insects.
Development
126
, 1091
–1101
Stewart
R. N.
, Semeniuk
P.
, Dermen
H.
(1974
) Competition and accommodation between apical layers and their derivatives in the ontogeny of chimeral shoots of Pelargonium X hortorum.
Am. J. Bot
61
, 54
–67
Struhl
G.
, Barbash
D.
, Lawrence
P. A.
(1997
) Hedgehog acts by distinct gradient and signal relay mechanisms to organise cell type and cell polarity in the Drosophila abdomen.
Development
124
, 2155
–2165
Struhl
G.
, Johnston
P.
, Lawrence
P. A.
(1992
) Control of Drosophila body pattern by the hunchback morphogen gradient.
Cell
69
, 237
–249
Stumpf
H. F.
(1966
) Mechanisms by which cells measure their position within the body.
Nature
212
, 430
–431
Sullivan
W.
(1987
) Independence of fushi tarazu expression with respect to cellular density in Drosophila embryos.
Nature
327
, 164
–167
Tsuge
T.
, Tsukaya
H.
, Uchimiya
H.
(1996
) Two independent and polarized processes of cell elongation regulate leaf blade expansion in Arabidopsisthaliana (L.) Heynh.
Development
122
, 1589
–1600
Usui
T.
, Shima
Y.
, Shimada
Y.
, Hirano
S.
, Burgess
R. W.
, Schwarz
T. L.
, Takeichi
M.
, Uemura
T.
(1999
) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled.
Cell
98
, 585
–595
van den Berg
C.
, Willemsen
V.
, Hage
W.
, Weisbeek
P.
, Scheres
B.
(1995
) Cell fate in the Arabidopsis root meristem determined by directional signalling.
Nature
378
, 62
–65
Vernon
J. A.
, Butsch
J.
(1957
) Effect of tetraploidy on learning and retention in the salamander.
Science
125
, 1033
–1034
Weigmann
K.
, Cohen
S. M.
, Lehner
C. F.
(1997
) Cell cycle progression, growth and patterning in imaginal discs despite inhibition of cell division after inactivation of Drosophila Cdc2 kinase.
Development
124
, 3555
–3563
Weinkove
D.
, Neufeld
T. P.
, Twardzik
T.
, Waterfield
M. D.
, Leevers
S. J.
(1999
) Regulation of imaginal disc cell size, cell number and organ size by Drosophila class IAphosphoinositide 3-kinase and its adaptor.
Curr. Biol
9
, 1019
–1029
Wigglesworth
V. B.
(1940
) Local and general factors in the development of ‘pattern’ in Rhodnius prolixus (Hemiptera).
J. Exp. Biol
17
, 180
–200
Williams
J. A.
, Paddock
S. W.
, Carroll
S. B.
(1993
) Pattern formation in a secondary field: a hierarchy of regulatory genes subdivides the developing Drosophila wing disc into discrete subregions.
Development
117
, 571
–584
Wolpert
L.
(1969
) Positional information and the spatial pattern of cellular differentiation.
J. Theor. Biol
25
, 1
–47
Zecca
M.
, Basler
K.
, Struhl
G.
(1995
) Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.
Development
121
, 2265
–2278
Zigmund
S. H.
(1981
) Consequences of chemotactic peptide receptor modulation for leukocyte orientation.
J. Cell Biol
88
, 644
–647
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