During Drosophila development, the salivary primordia are internalized to form the salivary gland tubes. By analyzing immuno-stained histological sections and scanning electron micrographs of multiple stages of salivary gland development, we show that internalization occurs in a defined series of steps, involves coordinated cell shape changes and begins with the dorsal-posterior cells of the primordia. The ordered pattern of internalization is critical for the final shape of the salivary gland. In embryos mutant for huckebein (hkb), which encodes a transcription factor, or faint sausage (fas), which encodes a cell adhesion molecule, internalization begins in the center of the primordia, and completely aberrant tubes are formed. The sequential expression of hkb in selected cells of the primordia presages the sequence of cell movements. We propose that hkb dictates the initial site of internalization, the order in which invagination progresses and, consequently, the final shape of the organ. We propose that fas is required for hkb-dependent signaling events that coordinate internalization.

Alvarez
I. S.
,
Navascues
J.
(
1990
)
Shaping, invagination, and closure of the chick embryo otic vesicle: scanning electron microscopic and quantitative study.
Anat. Rec
228
,
315
326
Andrew
D. J.
,
Baig
A.
,
Bhanot
P.
,
Smolik
S. M.
,
Henderson
K. D.
(
1997
)
The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle.
Development
124
,
181
193
Barrett
K.
,
Leptin
M.
,
Settleman
J.
(
1997
)
The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation.
Cell
91
,
905
915
Bowes
R. C.
3rd
,
Lightfoot
R. T.
,
Van De Water
B.
,
Stevens
J. L.
(
1999
)
Hepatocyte growth factor induces tubulogenesis of primary renal proximal tubular epithelial cells.
J. Cell Physiol
180
,
81
90
Brönner
G.
,
Chu-LaGraff
Q.
,
Doe
C. Q.
,
Cohen
B.
,
Weiogel
D.
,
Taubert
H.
,
Jäckle
H.
(
1994
)
Spi/egr-like zinc-finger protein required for endoderm specification and germ-layer formation in Drosophila.
Nature
369
,
664
668
Costa
M.
,
Wilson
E. T.
,
Wieschaus
E.
(
1994
)
A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation.
Cell
76
,
1075
89
Davies
J. A.
,
Bard
J. B.
(
1998
)
The development of the kidney.
Curr. Top. Dev. Biol
39
,
245
301
Ettensohn
C. A.
(
1985
)
Mechanisms of epithelial invagination.
Q. Rev. Biol
60
,
289
307
Flybase
(
1999
)
The FlyBase database of the Drosophila Genome Projects and community literature. The FlyBase Consortium.
Nucleic Acids Res
27
,
85
88
Glaser
O. R.
(
1916
)
The theory of autonomous folding in embryogenesis.
Science
44
,
505
509
Glazer
L.
,
Shilo
B.-Z.
(
1991
)
The Drosophila FGF-R homolog is expressed in the embryonic tracheal system and appears to be required for directed tracheal cell extension.
Genes Dev
5
,
697
705
Gudernatsch
J. F.
(
1913
)
Concerning the mechanism and direction of embryonic folding.
Anat. Rec
7
,
411
431
Gumbiner
B. M.
(
1992
)
Epithelial morphogenesis.
Cell
69
,
385
387
Haag
T. A.
,
Haag
N. P.
,
Lekven
A. C.
,
Hartenstein
V.
(
1999
)
The role of cell adhesion molecules in Drosophila heart morphogenesis: faint sausage, shotgun/DE-cadherin, and laminin A are required for discrete stages in heart development.
Dev. Biol
208
,
56
69
Hacker
U.
,
Lin
X.
,
Perrimon
N.
(
1997
)
The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis.
Development
124
,
3565
3573
Hacker
U.
,
Perrimon
N.
(
1998
)
DRhoGEF2 encodes a member of the Dbl family of oncogenes and controls cell shape changes during gastrulation in Drosophila.
Genes Dev
12
,
274
284
Hardin
J.
,
Keller
R.
(
1988
)
The behaviour and function of bottle cells during gastrulation of Xenopus laevis.
Development
103
,
211
30
Hilfer
S. R.
(
1983
)
Development of the eye of the chick embryo.
Scan Elect. Microsc
3
,
1353
1369
Hogan
B. L.
,
Yingling
J. M.
(
1998
)
Epithelial/mesenchymal interactions and branching morphogenesis of the lung.
Curr. Opin. Genet. Dev
8
,
481
6
Isaac
D. D.
,
Andrew
D. J.
(
1996
)
Tubulogenesis in Drosophila: a requirement for the trachealess gene product.
Genes Dev
10
,
103
117
Kjelsberg
C.
,
Sakurai
H.
,
Spokes
K.
,
Birchmeier
C.
,
Drummond
I.
,
Nigam
S.
,
Cantley
L. G.
(
1997
)
Met/ kidneys express epithelial cells that chemotax and form tubules in response to EGF receptor ligands.
Am. J. Physiol
272
,
222
228
Lane
M. C.
,
Koehl
M. A.
,
Wilt
F.
,
Keller
R.
(
1993
)
A role for regulated secretion of apical extracellular matrix during epithelial invagination in the sea urchin.
Development
117
,
1049
60
Lekven
A. C.
,
Tepass
U.
,
Keshmeshian
M.
,
Hartenstein
V.
(
1998
)
faint sausage encodes a novel extracellular protein of the immunoglobulin superfamily required for cell migration and the establishment of normal axonal pathways in the Drosophila nervous system.
Development
125
,
2747
2758
Leptin
M.
(
1999
)
Gastrulation in Drosophila: the logic and the cellular mechanisms.
EMBO J
18
,
3187
92
Leptin
M.
,
Grunewald
B.
(
1990
)
Cell shape changes during gastrulation in Drosophila.
Development
110
,
73
84
Liu
X.
,
Kiss
I.
,
Lengyel
J. A.
(
1999
)
Identification of genes controlling malpighian tubule and other epithelial morphogenesis in Drosophila melanogaster.
Genetics
151
,
685
695
Metzger
R. J.
,
Krasnow
M. A.
(
1999
)
Genetic control of branching morphogenesis.
Science
284
,
1635
1639
Montesano
R.
,
Matsumoto
K.
,
Nakamura
T.
,
Orci
L.
(
1991
)
Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor.
Cell
67
,
901
908
Montesano
R.
,
Schaller
G.
,
Orci
L.
(
1991
)
Induction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors.
Cell
66
,
697
711
Morize
P.
,
Christiansen
A. E.
,
Costa
M.
,
Parks
S.
,
Wieschaus
E.
(
1998
)
Hyperactivation of the folded gastrulation pathway induces specific cell shape changes.
Development
125
,
589
97
Odell
G. M.
,
Oster
G.
,
Alberch
P.
,
Burnside
B.
(
1981
)
The mechanical basis of morphogenesis. I. Epithelial folding and invagination.
Dev. Biol
85
,
446
62
Parks
S.
,
Wieschaus
E.
(
1991
)
The Drosophila gastrulation gene concertina encodes a G-like protein.
Cell
64
,
447
458
Reuter
R.
,
Panganiban
G. E. F.
,
Hoffmann
F. M.
,
Scott
M. P.
(
1990
)
Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos.
Development
110
,
1031
1040
Ridley
A. J.
(
1995
)
Rho-related proteins: actin cytoskeleton and cell cycle.
Curr. Opin. Genet. Dev
5
,
24
30
Sakurai
H.
,
Nigam
S. K.
(
1997
)
Transforming growth factor-beta selectively inhibits branching morphogenesis but not tubulogenesis.
Am. J. Physiol
272
,
139
146
Sakurai
H.
,
Tsukamoto
T.
,
Kjelsberg
C. A.
,
Cantley
L. G.
,
Nigam
S. K.
(
1997
)
EGF receptor ligands are a large fraction of in vitro branching morphogens secreted by embryonic kidney.
Am. J. Physiol
273
,
463
472
Sakurai
Y.
,
Sawada
T.
,
Chung
Y. S.
,
Funae
Y.
,
Sowa
M.
(
1997
)
Identification and characterization of motility stimulating factor secreted from pancreatic cancer cells: role in tumor invasion and metastasis.
Clin. Exp. Metastasis
15
,
307
317
Schoenwolf
G. C.
,
Smith
J. L.
(
1990
)
Mechanisms of neurulation: traditional viewpoint and recent advances.
Development
109
,
243
70
Smith
J. L.
,
Schoenwolf
G. C.
(
1988
)
Role of cell-cycle in regulating neuroepithelial cell shape during bending of the chick neural plate.
Cell Tissue Res
252
,
491
500
Smith
J. L.
,
Schoenwolf
G. C.
,
Quan
J.
(
1994
)
Quantitative analyses of neuroepithelial cell shapes during bending of the mouse neural plate.
J. Comp. Neurol
342
,
144
51
Smolik
S. M.
,
Rose
R. E.
,
Goodman
R. H.
(
1992
)
A cyclic AMP-responsive element-binding transcriptional activator in Drosophila melanogaster, dCREB-A, is a member of the leucine zipper family.
Mol. Cell Biol
12
,
4123
4131
Spriggs
M. K.
(
1999
)
Shared resources between the neural and immune systems: semaphorins join the ranks.
Curr. Opin. Immunol
11
,
387
91
Sutherland
D. C.
,
Samakovlis
C.
,
Krasnow
M. A.
(
1996
)
branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching.
Cell
87
,
1091
1101
Sweeton
D.
,
Parks
S.
,
Costa
M.
,
Wieschaus
E.
(
1991
)
Gastrulation in Drosophila: the formation of the ventral furrow and posterior midgut invaginations.
Development
112
,
775
89
Vainio
S.
,
Muller
U.
(
1997
)
Inductive tissue interactions, cell signaling, and the control of kidney organogenesis.
Cell
90
,
975
978
Vincent
S.
,
Ruberte
E.
,
Grieder
N. C.
,
Chen
C. K.
,
Haerry
T.
,
Schuh
R.
,
Affolter
M.
(
1997
)
DPP controls tracheal cell migration along the dorsoventral body axis of the Drosophila embryo.
Development
124
,
2741
50
Wappner
P.
,
Gabay
L.
,
Shilo
B.-Z.
(
1997
)
Interactions between the EGF receptor and DPP pathways establish distinct cell fates in the tracheal placodes.
Development
124
,
4707
4716
Wilk
R.
,
Weizman
I.
,
Shilo
B.-Z.
(
1996
)
trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila.
Genes Dev
10
,
93
102
Woolf
A. S.
,
Kolatsi-Joannou
M.
,
Hardman
P.
,
Andermarcher
E.
,
Moorby
C.
,
Fine
L. G.
,
Jat
P. S.
,
Nobel
M. D.
,
Gherardi
E.
(
1995
)
Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros.
J. Cell Biol
128
,
171
184
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