Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes.

Andrew, Deborah J.; Horner, Michael A.; Petitt, Matthew; Smolik, Sarah M.; Scott, Matthew P.

doi:10.1002/j.1460-2075.1994.tb06362.x

Cited by 112 publications

(98 citation statements)

References 84 publications

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“…When expressed throughout the embryo, Scr is able to induce an additional pair of salivary glands anterior to parasegment 2 (20), where the normal salivary glands form. Posteriorly its function is restricted by teashirt (tsh) and Abdominal-B (Abd-B) (26). In accordance with these findings, the wild type (Scr-HD wt ) and the constitutively active (Scr-HD AA ) synthetic genes could also induce ectopic salivary glands in the embryonic head, while the constitutively inactive variant (Scr-HD DD ) could not ( Fig.…”

Section: Resultssupporting

confidence: 75%

Function and specificity of synthetic Hox transcription factors in vivo

Papadopoulos

Vukojević

Adachi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Homeotic (Hox) genes encode transcription factors that confer segmental identity along the anteroposterior axis of the embryo. However the molecular mechanisms underlying Hox-mediated transcription and the differential requirements for specificity in the regulation of the vast number of Hox-target genes remain ill-defined. Here we show that synthetic Sex combs reduced (Scr) genes that encode the Scr C terminus containing the homedomain (HD) and YPWM motif (Scr-HD) are functional in vivo. Synthetic Scr-HD peptides can induce ectopic salivary glands in the embryo and homeotic transformations in the adult fly, act as transcriptional activators and repressors during development, and participate in protein-protein interactions. Their transformation capacity was found to be enhanced over their full-length counterpart and mutations known to transform the full-length protein into constitutively active or inactive variants behaved accordingly in the synthetic peptides. Our results show that synthetic Scr-HD genes are sufficient for homeotic function in Drosophila and suggest that the N terminus of Scr has a role in transcriptional potency, rather than specificity. We also demonstrate that synthetic peptides behave largely in a predictable way, by exhibiting Scr-specific phenotypes throughout development, which makes them an important tool for synthetic biology.synthetic genes | transcriptional specificity | Hox genes | Sex combs reduced | homeotic transformations H omeotic genes code for transcription factors that play an instrumental role in animal development by specifying the identity of body segments along the anteroposterior axis of the embryo (1-4). Hox genes have persisted in the animal kingdom; they are found in animals as diverse as worms and humans (5, 6) and the Homeodomain (HD), a helix-turn-helix DNA-binding domain, has been strikingly conserved in animals since before the bilaterian split (1,7,8). Sequence-specific binding of Hox proteins has been studied for the Drosophila Sex combs reduced (Scr) (9, 10), Antennapedia (Antp) (11, 12) and Ultrabithorax (Ubx) (11, 12) HDs. A consensus sequence TAATC/GC/G recognition core was identified in all of them, which alone is obviously not sufficient to confer transcriptional specificity, because it occurs statistically every kilobase in the genome. Similar sequence preferences have been identified for Deformed (Dfd) and Abdominal-B (Abd-B) (11), raising the question of how target specificity is achieved among different Hox paralogs.A closer look into conserved residues outside the HD identified its amino-terminal YPWM motif that is present in almost all Hox proteins, from flies to vertebrates [with the exception of Abdominal-B (Abd-B), which has conserved only the tryptophan at position 3] (13). Extradenticle (Exd) and its mammalian homolog Pbx1 (14) were found to interact specifically with the YPWM motif of Hox proteins in vitro (15) and crystallographic analysis of a Ubx-Exd complex determined the topology of this interaction (16). Recently the link between the Ant...

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Section: Resultssupporting

confidence: 75%

Function and specificity of synthetic Hox transcription factors in vivo

Papadopoulos

Vukojević

Adachi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In this regard, as the developmental stage for salivary gland formation approaches, there is no apparent change in the transcription of the Scr gene throughout the segment (Andrew et al, 1994). However, by mechanisms not yet understood, the product of the decapentaplegic (dpp) gene appears to establish a region of nonpermissibility in the dorsal portion of the two segments, yielding a dorsal limit of Scr activity (Panzer et al, 1992).…”

Section: (B) Early Processes (1) the Nature Of Regulatory Events In Ementioning

confidence: 99%

“…The tsh gene encodes a protein containing a zinc finger motif that is necessary for midgut formation (Mathies et al, 1994). In addition, as part of its role in the anterior thoracic segment, it inhibits the expression of Scr (Andrew et al, 1994). Thus, future salivary gland formation is limited only to relatively small areas on each side of the posterior head segment, bounded by dpp dorsally, dl-dependent products ventrally, and tsh posteriorly.…”

Section: (B) Early Processes (1) the Nature Of Regulatory Events In Ementioning

confidence: 99%

“…The dCREB-A protein is homologous with mammalian CREB, a transcription factor involved in signal transduction. Unlike fkh, dCREB-A transcription is first seen in Drosophila development at the restricted sites of salivary gland development, and may be under the direct control of the Scr gene (Andrew et al, 1994). The transcription of dCREB-A appears to continue to be exclusive to the salivary glands throughout the larval period, but is found in numerous tissues in the adult (Smolik et al, 1992).…”

Section: (B) Early Processes (1) the Nature Of Regulatory Events In Ementioning

confidence: 99%

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Salivary Glands: A Paradigm for Diversity of Gland Development

Denny

Ball

Redman

1997

Critical Reviews in Oral Biology & Medicine

177

171

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The major salivary glands of mammals are represented by three pairs of organs that cooperate functionally to produce saliva for the oral cavity. While each type of gland produces a signature secretion that complements the secretions from the other glands, there is also redundancy as evidenced by secretion of functionally similar and, in some cases, identical products in the three glands. This, along with their common late initiation of development, in fetal terms, their similarities in developmental pattern, and their proximate sites of origin, suggests that a common regulatory cascade may have been shared until shortly before the onset of overt gland development. Furthermore, occasional ectopic differentiation of individual mature secretory cells in the wrong" gland suggests that control mechanisms responsible for the distinctive cellular composition of each gland also share many common steps, with only minor differences providing the impetus for diversification. To begin to address this area, we examine here the origins of the salivary glands by reviewing the expression patterns of several genes with known morphogenetic potential that may be involved based on developmental timing and location. The possibility that factors leading to determination of the sites of mammalian salivary gland development might be homologous to the regulatory cascade leading to salivarv gland formation in Drosophila is also evaluated. In a subsequent section, cellular phenotypes of neonatal and adult glands are compared and evaluated for insights into the mechanisms and lineages leading to cellular diversification. Finally, the phenomena of proliferation, repair, and regeneration in adult salivary glands are reviewed, with emphasis on the extent to which the cellular diversity is reversible and which cell type other than stem cells has the ability to redifferentiate into other cell types.

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“…During embryogenesis, tsh has been shown to participate in the patterning of the epidermis (Fasano et al, 1991;Roder et al, 1992;Andrew et al, 1994;de Zulueta et al, 1994;Gallet et al, 1998Gallet et al, , 2000Robertson et al, 2004) and the development of the salivary glands (Henderson et al, 1999) and the gut (Mathies et al, 1994;Waltzer et al, 2001;Saller et al, 2002), and tsh null mutants are embryonic lethal (Fasano et al, 1991). The Drosophila genome contains also a tsh paralogue, tiptop (tio; Laugier et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Zinc‐finger paralogues tsh and tio are functionally equivalent during imaginal development in Drosophila and maintain their expression levels through auto‐ and cross‐negative feedback loops

Bessa

Carmona

Casares

2008

Developmental Dynamics

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teashirt (tsh) and tiptop (tio) are two Drosophila gene paralogues encoding zinc-finger transcription factors. While tsh is an important developmental regulator, tio null individuals are viable and fertile. Here, we show that tio and tsh have coincident expression domains in the imaginal discs, the precursors of the adult body, and that both genes show similar functional properties when expressed ectopically. Furthermore, tio is able to rescue the development of tsh mutants, indicating that both genes are functionally equivalent during imaginal development. Of interest, the transcriptional regulation of tio and tsh is linked by a negative feedback loop. This mechanism might be required to maintain a tight control on the total levels of tio/tsh and could help explaining why Drosophila keeps an apparently dispensable gene.

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Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes.

Cited by 112 publications

References 84 publications

Function and specificity of synthetic Hox transcription factors in vivo

Function and specificity of synthetic Hox transcription factors in vivo

Salivary Glands: A Paradigm for Diversity of Gland Development

Zinc‐finger paralogues tsh and tio are functionally equivalent during imaginal development in Drosophila and maintain their expression levels through auto‐ and cross‐negative feedback loops

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