Genes capable of translating positional information into regulated growth lie at the heart of morphogenesis, yet few genes with this function have been identified. Mutants in the Drosophila four-jointed (fj) gene show reduced growth and altered differentiation only within restricted sectors of the proximal-distal (PD) axis in the leg and wing, thus fj is a candidate for a gene with this coordination function. Consistent with a position-sensitive role, we show that fj is expressed in a regional pattern in the developing leg, wing, eye and optic lobe. The fj gene encodes a novel type II membrane glycoprotein. When the cDNA is translated in an in vitro translation system in the presence of exogenous microsomal membranes, the intralumenal portion of some of the molecules is cleaved, yielding a secreted C-terminal fragment. We propose that fj encodes a secreted signal that functions as a positive regulator of regional growth and differentiation along the PD axis of the imaginal discs.
Reference
Ashley
J. A.
, Katz
F. N.
(1994
) Competition and position-dependent targeting in the development of the Drosophila R7 visual projections.
Development
120
, 1537
–1547
Basler
K.
, Struhl
G.
(1994
) Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
Nature
368
, 208
–214
Bellen
H. J.
, O'Kane
C.J.
, Wilson
C.
, Grossniklaus
U.
, Pearson
R.K.
, Gehring
W. J.
(1989
) P-element-mediated enhancer detection: a versatile method to study development in Drosophila.
Genes Dev
3
, 1288
–1300
Bier
E.
, Vaessin
H.
, Shepherd
S.
, Lee
K.
, McCall
K.
, Barbel
S.
, Ackerman
L.
, Carretto
R.
, Uemura
T.
, Grell
E.
, Jan
L. Y.
, Jan
Y.N.
(1989
) Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector.
Genes Dev
3
, 1273
–1287
Boedigheimer
M.
, Laughon
A.
(1993
) expanded: a gene involved in the control of cell proliferation in imaginal discs.
Development
118
, 1291
–1301
Bryant
P. J.
(1993
) The polar coordinate model goes molecular.
Science
259
, 471
–472
Bryant
P. J.
, Huettner
B.
, Held
L. I.
, Ryerse
J.
, Szidonya
J.
(1988
) Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila.
Dev. Biol
129
, 541
–554
Buckles
G. R.
, Smith
Z. D. M.
, Katz
F. N.
(1992
) mip causes hyperinnervation of a retinotopic map in Drosophila by excessive recruitment of R7 photoreceptor cells.
Neuron
8
, 1015
–1029
Campbell
G.
, Weaver
T.
, Tomlinson
A.
(1993
) Axis specification in the developing Drosophila appendage: the role of wingless, decapentaplegic, and the homeobox gene aristaless.
Cell
74
, 113
–1123
Cavener
D. R.
, Ray
S. C.
(1991
) Eukaryotic start and stop translation sites.
Nucleic Acids Res
19
, 3185
–3192
Cohen
S. M.
, Bronner
G.
, Kuttner
F.
, Jurgens
G.
, Jackle
H.
(1989
) Distal-less encodes a homoeodomain protein required for limb development in Drosophila.
Nature
338
, 432
–434
Couso
J. P.
, Bate
M.
, Martinez-Arias
A.
(1993
) A wingless -dependent polar coordinate system in Drosophila imaginal discs.
Science
259
, 484
–489
Deng
Y.
, Rizki
T. M.
(1988
) Genetic and developmental analysis of the A1 phenoloxidase of Drosophila.
Genome
30
, 192
–.Diaz-Benjumea
F. J.
, Cohen
B.
, Cohen
S. M.
(1994
) Cell interaction between compartments establishes the proximal-distal axis of Drosophila legs.
Nature
372
, 175
–179
Eipper
B. A.
, Stoffers
D. A.
, Mains
R. E.
(1992
) The biosynthesis of neuropeptides: peptide-amidation.
Annu. Rev. Neurosci
15
, 57
–85
Godt
D.
, Couderc
J. L.
, Cramton
S. E.
, Laski
F. A.
(1993
) Pattern formation in the limbs of Drosophila: bric a brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus.
Development
119
, 799
–812
Hartmann
E.
, Rapoport
T. A.
, Lodish
H. F.
(1989
) Predicting the orientation of eukaryotic membrane-spanning proteins.
Proc. Natl. Acad. Sci. USA
86
, 5786
–5790
Hortsch
M.
, Goodman
C. S.
(1991
) Cell and substrate adhesion molecules in Drosophila.
Ann. Rev. Cell Biol
7
, 505
–557
Kunes
S.
, Wilson
C.
, Steller
H.
(1993
) Independent guidance of retinal axons in the visual system of Drosophila.
J. Neurosci
13
, 752
–767
Kyte
J.
, Doolittle
R. F.
(1982
) A simple method for displaying the hydropathic character of a protein.
J. Mol. Biol
157
, 133
–148
Lee
J. J.
, von Kessler
D. P.
, Parks
S.
, Beachy
P. A.
(1992
) Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog.
Cell
71
, 33
–50
Mahoney
P. A.
, Weber
U.
, Onofrechuk
P.
, Biessmann
H.
, Bryant
P.J.
, Goodman
C. S.
(1991
) The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily.
Cell
67
, 853
–868
Mardon
G.
, Solomon
N. M.
, Rubin
G. M.
(1994
) dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila.
Development
120
, 3473
–3486
Massague
J.
, Pandiella
A.
(1993
) Membrane-anchored growth factors.
Annu. Rev. Biochem
62
, 515
–541
Ready
D. F.
, Hansen
T. J. E.
, Benzer
S.
(1976
) Development of the Drosophila retina, a neurocrystalline lattice.
Dev. Biol
53
, 217
–240
Robertson
H. M.
, Preston
C. R.
, Phillis
R. W.
, Johnson-Schlitz
D. M.
, Benz
W. K.
, Engels
W. R.
(1988
) A stable genomic source of P element transposase in Drosophila melanogaster.
Genetics
118
, 461
–470
Rogers
S.
, Wells
R.
, Rechsteiner
M.
(1986
) Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis.
Science
234
, 364
–368
Schneitz
K.
, Spielmann
P.
, Noll
M.
(1993
) Molecular genetics of aristaless, a prd-type homeo box gene involved in the morphogenesis of proximal and distal pattern elements in a subset of appendages in Drosophila.
Genes Dev
7
, 114
–129
Smith
J. C.
(1994
) Hedgehog, the floor plate, and the zone of polarizing activity.
Cell
76
, 193
–196
Tabata
T.
, Kornberg
T. B.
(1994
) Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs.
Cell
76
, 89
–102
Tokunaga
C.
, Gerhart
J. C.
(1976
) The effect of growth and joint formation on bristle pattern in D. melanogaster. J. Exp.
Zool
198
, 79
–96
Van Vactor
D. L.
Jr., Cagan
R. L.
, Kramer
H.
, Zipursky
S. L.
(1991
) Induction in the developing compound eye of Drosophila: multiple mechanisms restrict R7 induction to a single retinal precursor cell.
Cell
67
, 1145
–1155
von Heijne
G.
(1986
) A new method for predicting signal sequence cleavage sites.
Nucleic Acids Res
14
, 4683
–4690
Waddington
C. H.
(1943
) The development of some ‘leg genes’ in Drosophila.
J. Genet
45
, 29
–43
Walter
P.
, Blobel
G.
(1983
) Preparation of microsomal membranes for cotranslational protein translocation.
Meth. Enzymol
96
, 682
–691
Wilson
C.
, Pearson
R. K.
, Bellen
H. J.
, O'Kane
C. J.
, Grossniklaus
U.
, Gehring
W. J.
(1989
) P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila.
Genes Dev
3
, 1301
–1313
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