We describe the direct and cell-specific regulation of the Drosophila FMRFa neuropeptide gene by Apterous, a LIM homeodomain transcription factor. dFMRFa and Apterous are expressed in partially overlapping subsets of neurons, including two of the seventeen dFMRFa cell types, the Tv neuroendocrine cells and the SP2 interneurons. Apterous contributes to the initiation of dFMRFa expression in Tv neurons, but not in those dFMRFa neurons that do not express Apterous. Apterous is not required for Tv neuron survival or morphological differentiation. Apterous contributes to the maintenance of dFMRFa expression by postembryonic Tv neurons, although the strength of its regulation is diminished. Apterous regulation of dFMRFa expression includes direct mechanisms, although ectopic Apterous does not induce ectopic dFMRFa. These findings show that, for a subset of neurons that share a common neurotransmitter phenotype, the Apterous LIM homeoprotein helps define neurotransmitter expression with very limited effects on other aspects of differentiation.

Ahlgren
U.
,
Pfaff
S. L.
,
Jessell
T. M.
,
Edlund
T.
,
Edlund
H.
(
1997
)
Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells.
Nature
385
,
257
260
Altaratz
M.
,
Applebaum
S. W.
,
Richard
D. S.
,
Gilbert
L. I.
,
Segal
D.
(
1991
)
Regulation of juvenile hormone synthesis in wild-type and apterous mutant Drosophila.
Mol. Cell. Endocrinol
8
,
205
216
Biggin
M. D.
,
McGinnis
W.
(
1997
)
Regulation of segmentation and segmental identity by Drosophila homeoproteins: the role of DNA binding in functional activity and specificity.
Development
124
,
4425
4433
Blair
S. S.
,
Brower
D. L.
,
Thomas
J. B.
,
Zavortink
M.
(
1994
)
The role of apterous in the control of dorso-ventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila.
Development
120
,
1805
1814
Bourgouin
C.
,
Lundgren
S. E.
,
Thomas
J. B.
(
1992
)
apterous is a Drosophila LIM domain gene required for the development of a subset of embryonic muscles.
Neuron
9
,
549
561
Calleja
M.
,
Moreno
E.
,
Pelaz
S.
,
Morata
G.
(
1996
)
Visualization of gene expression in living adult Drosophila.
Science
274
,
252
255
Capovilla
M.
,
Brandt
M.
,
Botas
J.
(
1994
)
Direct regulation of decapentaplegic by Ultrabithorax and its role in Drosophila midgut morphogenesis.
Cell
76
,
461
475
Chin
A.
,
Reynolds
E.
,
Scheller
R. H.
(
1990
)
Organization and expression of the Drosophila FMRFamide-related prohormone gene.
DNA Cell Biol
9
,
263
271
Cohen
B.
,
McGuffin
M. E.
,
Pfeifle
C.
,
Segal
D.
,
Cohen
S. M.
(
1992
)
apterous, a gene required for imaginal disc development in Drosophila, encodes a member of the LIM family of developmental regulatory proteins.
Genes. Dev
6
,
715
729
Curtiss
J.
,
Heilig
J. S.
(
1998
)
DeLIMiting development.
BioEssays
20
,
58
69
Desai
C.
,
Garriga
G.
,
McIntire
S. L.
,
Horvitz
H. R.
(
1988
)
A genetic pathway for the development of the Caenorhabditis elegans HSN motorneurons.
Nature
3366
,
38
646
Diaz-Benjumea
F. J.
,
Cohen
S. M.
(
1993
)
Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila.
Cell
75
,
741
752
Gehring
W. J.
,
Qian
Y. Q.
,
Billeter
M.
,
Furukubo-Tkunaga
K.
,
Schier
A. F.
,
Resendez-Perez
D.
,
Affolter
M.
,
Otting
G.
,
Wuthrich
K.
(
1994
)
Homeodomain-DNA recognition.
Cell
78
,
211
223
Gorczyca
M. G.
,
Phillis
R. W.
,
Budnik
V.
(
1994
)
The role of tinman, a mesodermal cell fate gene, in axon pathfinding during the development of the transverse nerve in Drosophila.
Development
120
,
2143
2152
Hobert
O.
,
Mori
I.
,
Yamashita
Y.
,
Honda
H.
,
Ohshima
Y.
,
Liu
Y.
,
Ruvkun
G.
(
1997
)
Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene.
Neuron
19
,
345
357
Jin
Y.
,
Hoskins
R.
,
Horvitz
H. R.
(
1994
)
Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein.
Nature
372
,
780
783
Johnson
W. A.
,
Hirsh
J.
(
1990
)
Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons.
Nature
343
,
467
470
Karlsson
O.
,
Thor
S.
,
Norberg
T.
,
Ohlsson
H.
,
Edlund
T.
(
1990
)
Insulin gene binding protein Isl-1 is a member of a novel class of proteins containing both a homeo-and a Cys-His domain.
Nature
344
,
879
882
Lichtsteiner
T.
,
Tjian
R.
(
1995
)
Synergistic activation of transcription by UNC-86 and MEC-3 in Caenorhabditis elegans embryo extracts.
EMBO J
14
,
3937
3945
Lo
L.
,
Tiveron
M.-C.
,
Anderson
D. J.
(
1998
)
MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity.
Development
125
,
609
620
Lundell
M. J.
,
Hirsh
J.
(
1992
)
The zfh-2 gene product is a potential regulator of neuron-specific DOPA decarboxylase gene expression in Drosophila.
Dev. Biol
154
,
84
94
Lundgren
S. E.
,
Callahan
C. A.
,
Thor
S.
,
Thomas
J. B.
(
1995
)
Control of neuronal pathway selection by the Drosophila LIM homeodomain gene apterous.
Development
121
,
1769
1773
Morcillo
P.
,
Rosen
C.
,
Baylies
M. K.
,
Dorsett
D.
(
1997
)
Chip, a widely expressed chromosomal protein required for segmentation andactivity of a remote wing margin enhancer in Drosophila.
Genes Dev
11
,
2729
2740
O'Brien
M. A.
,
Schneider
L. E.
,
Taghert
P. H.
(
1991
)
In situ hybridization analysis of the FMRFamide neuropeptide gene in Drosophila. II. Constancy in the cellular pattern of expression during metamorphosis.
J. Comp. Neurol
304
,
623
638
O'Keefe
D. D.
,
Thor
S.
,
Thomas
J. B.
(
1998
)
Function and specificity of LIM domains in Drosophila nervous system and wing development.
Development
125
,
3915
3923
Pfaff
S. L.
,
Medelsohn
C. L.
,
Stewart
C. L.
,
Edlund
T.
,
Jessel
T. M.
(
1996
)
A requirement for the LIM homeobox gene isl-1 in motorneuron generation reveals a motorneuron-dependent step in the differentiation of ventral interneurons.
Cell
84
,
309
320
Pfaff
S.
,
Kintner
C.
(
1998
)
Neuronal diversification: development of motor neuron subtypes.
Current Opin. Neurobiol
8
,
27
36
Porter
F. D.
,
Drago
J.
,
Xu
Y.
,
Cheema
S. S.
,
Wassif
C.
,
Huang
S. P.
,
Lee
E.
,
Grinberg
A.
,
Massala
J. S.
,
Bodine
D.
,
Alt
F.
,
Westphal
H.
(
1997
)
Lhx2, a LIM homeodomain gene, is required for eye, forebrain and definitive erythrocyte development.
Development
124
,
2935
2944
Schneider
L. E.
,
O'Brien
M. A.
,
Taghert
P. H.
(
1991
)
In situ hybridization analysis of the FMRFamide neuropeptide gene in Drosophila. I. Restricted expression in embryonic and larval stages.
J. Comp. Neurol
304
,
608
622
Schneider
L. E.
,
Roberts
M. S.
,
Taghert
P. H.
(
1993
)
Cell type-specific transcriptional regulation of the Drosophila FMRFamide neuropeptide gene.
Neuron
10
,
279
291
Small
S.
,
Kraut
R.
,
Hoey
T.
,
Warrior
R.
,
Levine
M.
(
1991
)
Transcriptional regulation of a pair-rule stripe in Drosophila.
Genes Dev
5
,
827
839
Stevens
M. E.
,
Bryant
P. J.
(
1986
)
Temperature-dependent expression of the apterous phenotype in Drosophila melanogaster.
Genetics
112
,
217
228
Struhl
G.
,
Struhl
K.
,
MacDonald
P. M.
(
1989
)
The gradient morphogen Bicoid is a concentration-dependent transcriptional activator.
Cell
57
,
1259
1273
Taghert
P. H.
,
Schneider
L. E.
(
1990
)
Interspecific comparison of a Drosophila gene encoding FMRFamide-related neuropeptides.
J. Neurosci
10
,
1929
1942
Thor
S.
,
Ericson
J.
,
Brannstrom
T.
,
Edlund
T.
(
1991
)
The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat.
Neuron
7
,
881
889
Thor
S.
,
Thomas
J. B.
(
1997
)
The Drosophila islet gene governs axonal pathfinding and neurotransmitter identity.
Neuron
18
,
397
409
Tsuchida
T.
,
Ensini
M.
,
Morton
S. B.
,
Baldasarre
M.
,
Edlund
T.
,
Jessell
T.
,
Pfaff
S.
(
1994
)
Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.
Cell
79
,
957
970
Wang
M.
,
Drucker
D. J.
(
1995
)
The LIM domain homeobox gene isl-1 is a positive regulator of islet cell-specific proglucagon gene transcription.
J. Biol. Chem
270
,
12646
12652
Way
J. C.
,
Chalfie
M.
(
1988
)
Mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans.
Cell
54
,
5
16
Xue
D.
,
Tu
Y.
,
Chalfie
M.
(
1993
)
Cooperative interactions between the Caenorhabditis elegans homeoproteins Unc-86 and Mec-3.
Science
261
,
1324
1328
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