Drosophila T box proteins break the symmetry of hedgehog-dependent activation of wingless.
BACKGROUND
Segmentation of the Drosophila embryo is a classic paradigm for pattern formation during development. The Wnt-1 homolog Wingless (Wg) is a key player in the establishment of a segmentally reiterated pattern of cell type specification. The intrasegmental polarity of this pattern depends on the precise positioning of the Wg signaling source anterior to the Engrailed (En)/Hedgehog (Hh) domain. Proper polarity of epidermal segments requires an asymmetric response to the bidirectional Hh signal: wg is activated in cells anterior to the Hh signaling source and is restricted from cells posterior to this signaling source.


RESULTS
Here we report that Midline (Mid) and H15, two highly related T box proteins representing the orthologs of zebrafish hrT and mouse Tbx20, are novel negative regulators of wg transcription and act to break the symmetry of Hh signaling. Loss of mid and H15 results in the symmetric outcome of Hh signaling: the establishment of wg domains anterior and posterior to the signaling source predominantly, but not exclusively, in odd-numbered segments. Accordingly, loss of mid and H15 produces defects that mimic a wg gain-of-function phenotype. Misexpression of mid represses wg and produces a weak/moderate wg loss-of-function phenocopy. Furthermore, we show that loss of mid and H15 results in an anterior expansion of the expression of serrate (ser) in every segment, representing a second instance of target gene repression downstream of Hh signaling in the establishment of segment polarity.


CONCLUSIONS
The data we present here indicate that mid and H15 are important components in pattern formation in the ventral epidermis. In odd-numbered abdominal segments, Mid/H15 activity plays an important role in restricting the expression of Wg to a single domain.
Medical Research Council Centre for Developmental Neurobiology, King's College London, 4th Floor New Hunts House, Guy's Hospital Campus, London SE1 1UL, UK. marita.buescher@kcl.ac.uk
Marita
M
Buescher
Pia C
PC
Svendsen
Murni
M
Tio
Cindy
C
Miskolczi-McCallum
Guy
G
Tear
William J
WJ
Brook
William
W
Chia
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002135:Calcium-Binding Proteins; D003001:Cloning, Molecular; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D051155:Wnt1 Protein
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; C495572:H15 protein, Drosophila; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D020825:T-Box Domain Proteins; D051155:Wnt1 Protein; C495571:mid protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila