tailless
Tailless mRNA is found in the blastoderm stage [Images]. Initial activation of tll transcription is in two mirror image symmetrical caps at the poles of the embryo. This expression resolves into a posterior cap and an anterior-dorsal stripe. tll is also expressed in brain neuroblasts (Pignoni, 1990).
Early tailless expression (blastoderm stage) covers the anlage of the entire brain. Beginning approximately with the onset of gastrulation, an anterior-dorsal region with a high expression level (called HL domain) can be distinguished from a posterior-ventral domain expressing tll at a somewhat lower level. The HL domain coincides with part of the central and anterior protocerebral neurectoderm. The low expression level LL domain covers the remaining part of the protocerebral neuroectoderm. orthodenticle is expressed in a circumferential domain of the cellular blastoderm but during gastrulation becomes restricted to a domain that encompasses most of the protocerebral neurectoderm and an adjacent part of the deuterocerebral neurectoderm. All neurobasts segregating from this domain transiently express otd during stages 10 and 11. buttonhead is initially expressed in a wide domain including the anlagen of the antennal, intercalary and mandibular segments, as well as the acron. With the beginning of gastrulation, expression disappears from most of the procephalon, except for small domains of the posterior part of the deuterocerebral and tritocerebral neurectoderm and a dorsoanterior patch that partially overlaps with the dorsoanterior protocerebrum. Both the late deutocerebral and tritocerebral btd domains contain few, if any neuroblasts. empty spiracles is in an asymmetric circumferential domain of the cellular blastoderm. During gastrulation, this pattern resolves into two stripes that occupy anterior portions of the deuterocerebral neuroectoderm and the mandibular metamere, respectively. In addition, a small circular domain corresponding to the tritocerebral neurectoderm appears ventral to the deuterocerebral stripe (Younossi-Hartenstein, 1997).
Loss of tll function results in the absence of all protocerebral neuroblasts and loss of all four coherent domains of Fas II expression in the protocerebrum. Also missing is the optic lobe. orthodenticle functions in a domain that includes a large part of the protocerebrum and a smaller part of the adjacent deuterocerebrum. Loss of otd results in loss of protocerebral P1, P2 and P4 coherent domains of Fas II expression. Also missing is a nerve that carries axons from the antennal organ. In buttonhead mutation the D/T cluster is missing; consequently a cervical connection is missing that normally sends nerves to the labral sensory organ, the hypopharyngeal sensory organ and the stomatogastric nervous system (Younossi-Hartenstein, 1997).
The Drosophila brain develops from the procephalic neurogenic region of the ectoderm. About 100 neural precursor cells (neuroblasts) delaminate from this region on either side in a reproducible spatiotemporal pattern. Neuroblast maps have been prepared from different stages of the early embryo (stages 9, 10 and 11, when the entire population of neuroblasts has formed), in which about 40 molecular markers representing the expression patterns of 34 different genes are linked to individual neuroblasts. In particular, a detailed description is presented of the spatiotemporal patterns of expression in the procephalic neuroectoderm and in the neuroblast layer of the gap genes empty spiracles, hunchback, huckebein, sloppy paired 1 and tailless; the homeotic gene labial; the early eye genes dachshund, eyeless and twin of eyeless; and several other marker genes (including castor, pdm1, fasciclin 2, klumpfuss, ladybird, runt and unplugged). Based on the combination of genes expressed, each brain neuroblast acquires a unique identity, and it is possible to follow the fate of individual neuroblasts through early neurogenesis. Furthermore, despite the highly derived patterns of expression in the procephalic segments, the co-expression of specific molecular markers discloses the existence of serially homologous neuroblasts in neuromeres of the ventral nerve cord and the brain. Taking into consideration that all brain neuroblasts are now assigned to particular neuromeres and individually identified by their unique gene expression, and that the genes found to be expressed are likely candidates for controlling the development of the respective neuroblasts, these data provide a basic framework for studying the mechanisms leading to pattern and cell diversity in the Drosophila brain, and for addressing those mechanisms that make the brain different from the truncal CNS (Urbach, 2003).
The cephalic gap genes are expressed in large domains of the procephalon and play a crucial role not only in the patterning of the peripheral ectoderm, but also in regionalizing the brain primordium. The segmental organization of the Drosophila brain is based on the expression pattern of segment polarity and DV patterning genes. To see whether the cephalic gap genes respect the neuromeric boundaries segment polarity and DV patterning genes, and to provide a basis for studying their potential role in the formation or specification of brain precursor cells, the expression was studied of orthodenticle, empty spiracles, sloppy paired 1, tailless, huckebein, and hunchback in the developing head ectoderm, as well as in the entire population of identified NBs during stages 9-11 (Urbach, 2003).
tailless (tll) has been shown to be expressed in an anterior horseshoe-shaped stripe in the cellular blastoderm, which after gastrulation shows a region of high ('HL domain') and a region of low level of tll expression ('LL domain'), and at stage 9 covers most of the protocerebral neuroectoderm. Using a tll-lacZ line at stage 9 tll expression has been found in the developing brain in most protocerebral NBs (except the dorsoposterior ones). During stages 9-11 tll-lacZ expression expands in the protocerebral neuroectoderm beyond the En-positive head spot (hs). By stage 11 it is detectable in all protocerebral NBs. In addition, tll-lacZ is found in some ventral and dorsal deutocerebral NBs, indicating that tll is not exclusively confined to protocerebral progenitors (Urbach, 2003).
The development of the head and tail regions of the Drosophila embryo is dependent upon the localized polar activation of Torso (Tor), a receptor tyrosine kinase that is uniformly distributed in the membrane of the developing embryo. Trunk (Trk), the proposed ligand for Tor, is secreted as an inactive precursor into the perivitelline fluid that lies between the embryonic membrane and the vitelline membrane (VM), the inner layer of the eggshell. The spatial regulation of Trk processing is thought to be mediated by the secreted product of the torsolike (tsl) gene, which is expressed during oogenesis by a specialized population of follicle cells present at the two ends of the oocyte. Tsl protein has been shown to be specifically localized to the polar regions of the VM in laid eggs. Although Tsl can associate with nonpolar regions of the VM, the activity of polar-localized Tsl is enhanced, suggesting the existence of another spatially restricted factor acting in this pathway. The incorporation of Tsl into the VM provides a mechanism for the transfer of spatial information from the follicle cells to the developing embryo. Tsl represents the first example of an embryonic patterning determinant that is a component of the eggshell (Stevens, 2003).
Activation of Tsl may be spatially regulated through the action of gap genes. Spatial regulation of the expression of the gap genes, the first zygotic patterning genes to be expressed during embryogenesis, is determined by the activity of the three maternal pathways (anterior, posterior, and terminal) required for the development of the anterior-posterior axis of the embryo. In addition to localized maternal input, interactions between the gap gene products themselves led to further refinement of their expression domains. tll expression, for example, is specifically repressed in the segmented region of the embryo by central gap gene products such as Kr. Thus, depending on their relative levels of activity, Kr and Tll are both capable of suppressing one another's expression. This raises the possibility that centrally expressed Kr is responsible for the polar restriction of tll expression that is observed in the progeny of tsl mutant females expressing tsl from the germline. To address this question, the CBBtsl insertion was crossed into females that were mutant for all three anterior-posterior maternal pathways. Embryos produced by mothers triply mutant for bicoid (anterior), oskar (posterior), and tsl (terminal) lack all anterior-posterior patterning, express low levels of Kr uniformly along the anterior-posterior axis, and do not express tll at all. In contrast, the embryos produced by triply mutant females carrying CBBtsl did express tll in distinct polar domains, either at the anterior alone or at both poles. Consistent with this pattern of tll expression, Kr expression is specifically repressed in the corresponding polar domains. Further, these embryos also differentiate Filzkörper material, a posterior cuticular structure that requires terminal pathway activity, at one or both poles. Thus, although Tsl was distributed uniformly in their VMs, these embryos developed gap gene expression patterns and cuticular phenotypes consistent with polar activation of the Tor receptor. These findings suggest that the activity of Tsl is enhanced at, and perhaps restricted to, the polar regions of the VM; this finding implies that there is an as yet unidentified component of the terminal class pathway that is restricted to the poles and is required for the function of Tsl (Stevens, 2003).
The existence of another localized factor in this pathway indicates that there are at least four levels of control that ensure the polar restriction of tll expression during embryonic development. (1) First to act is the restriction of tsl expression to a specific subpopulation of follicle cells present at the poles of the oocyte. (2) Next is the stabilization of secreted Tsl protein at the poles of the VM and its incorporation into the eggshell in an active form. (3)The facilitation of Tsl function follows, through its proposed interaction with another localized factor. (4)The final layer of control is the exclusion of tll expression from nonpolar regions through the inhibitory effects of centrally expressed gap genes. Although it has long been assumed that the spatial restriction of tsl expression was the uniquely localized element in the terminal pathway, data is presented implying the existence of another factor that enhances the activity of Tsl specifically at the poles. The function of Tsl itself is unknown, and there are currently no candidate genes encoding proteins with the enzymatic activity to bring about the proposed processing of the Trk precursor. It is likely, therefore, that the identification of this factor will greatly enhance understanding of the mechanism by which the Tor ligand is formed (Stevens, 2003).
Drosophila segmentation is governed by a well-defined gene regulation network. The evolution of this network was investigated by examining the expression profiles of a complete set of segmentation genes in the early embryos of the mosquito, Anopheles gambiae. There are numerous differences in the expression profiles as compared with Drosophila. The germline determinant Oskar is expressed in both the anterior and posterior poles of Anopheles embryos but is strictly localized within the posterior plasm of Drosophila. The gap genes hunchback and giant display inverted patterns of expression in posterior regions of Anopheles embryos, while tailless exhibits an expanded pattern as compared with Drosophila. These observations suggest that the segmentation network has undergone considerable evolutionary change in the dipterans and that similar patterns of pair-rule gene expression can be obtained with different combinations of gap repressors. The evolution of separate stripe enhancers in the eve loci of different dipterans is discussed (Goltsev, 2004).
In Drosophila, different levels of the Hunchback and Knirps gap repressor gradients define the limits of eve stripes 3, 4, 6, and 7, while Giant and Kruppel establish the borders of stripes 2 and 5. In situ hybridization probes were prepared for Anopheles orthologues of all four of these gap genes, as well as a fifth gap gene, tailless. hunchback displays a broad band of expression in the anterior half of the Anopheles embryo, encompassing both the presumptive head and thorax. This pattern is similar to that observed in Drosophila, although there are a few notable deviations: (1) there is no obvious maternal expression seen in early Anopheles embryos, whereas maternal hunchback mRNAs are strongly expressed throughout early Drosophila embryos; (2) there is a significant change in the posterior staining pattern. The Drosophila gene displays a strong posterior stripe of expression that is comparable in intensity to the anterior staining pattern. In Anopheles, this staining is significantly weaker than that of the anterior domain, and the posterior pattern is shifted anteriorly into the presumptive abdomen (Goltsev, 2004).
The Kruppel and knirps staining patterns are similar in Anopheles and Drosophila embryos. In both cases, the principal sites of expression are seen in the presumptive thorax and abdomen, respectively. However, the remaining two gap genes, giant and tailless, exhibit distinctive staining patterns. In Anopheles, giant exhibits a continuous band of staining in anterior regions, whereas the Drosophila gene is excluded from the anterior pole. Moreover, there is a prominent band of staining in the presumptive abdomen of Drosophila embryos that is not seen in Anopheles. Finally, tailless is expressed in a narrow stripe in the posterior pole of Drosophila embryos, whereas Anopheles embryos display a dynamic pattern that (transiently) extends throughout the presumptive abdomen (Goltsev, 2004).
The altered patterns of hunchback and giant expression in posterior regions raise the possibility that different combinations of gap repressors are used to establish eve stripes 5, 6, and 7 in Anopheles and Drosophila. It is unlikely that Giant establishes the posterior border of eve stripe 5 and that Hunchback delimits the posterior border of stripe 7, as seen in Drosophila. The expression profiles of additional gap genes were analyzed in an effort to identify potential repressors for these stripe borders. The most obvious candidates are huckebein and tailless, since both are expressed in the posterior pole of Drosophila embryos. No expression of huckebein was seen in early embryos, although strong staining appears after germband elongation (Goltsev, 2004).
The gap gene tailless is initially detected at the anterior and posterior poles, with roughly equivalent levels of staining at the two sites. At slightly later stages, the anterior domain is lost, and the posterior pattern expands throughout the presumptive abdomen. The tailless transcripts detected in posterior regions exhibit a graded distribution, with peak levels at the posterior pole and progressively lower levels in more anterior regions. During cellularization, staining is reduced in posterior regions and reappears near the anterior pole. This broad and dynamic staining pattern is consistent with the possibility that the Tailless repressor specifies the posterior borders of one or more posterior eve stripes (Goltsev, 2004).
Torso signaling was examined in the Anopheles embryo in an effort to understand the basis for the expanded tailless expression pattern. In Drosophila, tailless is activated by the Torso signaling pathway, which can be visualized with an antibody against diphospho (dp)-ERK. The antibody detects localized staining in the terminal regions of early Drosophila embryos. A similar staining pattern is detected in Anopheles, although staining may be somewhat broader in Anopheles than Drosophila. It is therefore conceivable that the expansion of the posterior tailless expression pattern seen in Anopheles might be due to an expanded activation of the Torso signaling pathway (Goltsev, 2004).
In Drosophila, eve stripes 6 and 7 are regulated by different concentrations of Knirps and Hunchback. Low levels of Knirps define the anterior border of stripe 7, while higher levels are needed to repress eve stripe 6. Conversely, low levels of Hunchback establish the posterior border of eve stripe 6, while higher levels regulate stripe 7. The position of the knirps expression pattern is consistent with the possibility that it defines the anterior limits of stripes 6 and 7, just as in Drosophila. However, the posterior borders of these stripes are probably not regulated by Hunchback. The expanded pattern of tailless expression seen in Anopheles might permit it to establish the posterior border of eve stripe 6 and possibly stripe 7. An alternative candidate for the posterior stripe 7 border is giant, which is expressed in a tight domain within the posterior pole. Consistent with this possibility is the observation that the posterior giant pattern comes on relatively late, and the posterior stripe 7 border is the last to form among the seven eve stripes. The reversal of the posterior hunchback and giant expression patterns, along with the expanded tailless pattern, strongly suggests that different combinations of gap repressors are used to define eve stripes 5, 6, and 7 in Drosophila and Anopheles (Goltsev, 2004).
tailless mutants exhibit deletions in the terminal (anterior and posterior) domains of the embryo. There is a correlation between the presence of the posterior cap of tll expression and differentiation of a telson. In the anterior the maternal anterior system, Bicoid is required together with the terminal system and its target tailless to establish the acron (Pignoli, 1992). tailless is responsible in the tail for hindgut and Malpighian tubules and a large portion of the posterior midgut, hindgut and anal pads.
In mutants of huckebein and tailless, genes known to specify, respectively, adjacent posterior and anterior domains of the posterior midgut invagination, folded gastrulation transcription at the posterior pole does not extend as far anteriorly. The same lack of extention is evident in forkhead mutants. The double mutant huckebein tailless is the only double mutant combination of these three genes that completely eliminates the posterior midgut invagination; this combination also abolishes all expression of fog at the posterior pole. It is not clear how the anterior extent of fog transcription is delimited, since the domain of tailless expression and activity extends further to the anterior than the region of fog expression (Costa, 1994).
tailless mutations have little effect on hindsight expression; from analysis of huckebein tailless double mutants, it is clear that the only loss of Hnt protein expression in tailless mutants occurs in the region from which the Malpighian tubule primordia originate, consistent with the reported role for tll and hnt in the development of these structures. hkb mutant embryos lack Hnt protein expression in the regions from which the anterior and posterior midgut normally arise; expression remains only in the presumptive ureter of the Malpighian tubules. In hkb tll double mutant embryos, Hnt protein is not present at all in the domains that would form anterior and posterior midgut and Malpighian tubule primordia; however expression does occur in the amnioserosa. Germ-band retraction occurs in tll or hkb single mutants as well as in hkb tll double mutants, suggesting that midgut expression of Hnt is not necessary for germ-band retraction (Yip, 1997).
Mammalian cell culture studies have shown that several members of the nuclear receptor super family such as glucocorticoid receptor, retinoic acid receptor and
thyroid hormone receptor can repress the activity of AP-1 proteins (referring to Drosophila Kayak and Jun) by a mechanism that does not require the nuclear receptor to bind to DNA directly, but that is
otherwise poorly understood. Several aspects of nuclear receptor function are believed to rely on this inhibitory mechanism, which is referred to as transrepression.
This study presents evidence that nuclear receptor-mediated transrepression of AP-1 occurs in Drosophila melanogaster. In two different developmental situations,
embryonic dorsal closure and wing development, several nuclear receptors, including Seven up, Tailless, and Eagle antagonize AP-1. The inhibitory interactions with
nuclear receptors are integrated with other modes of AP-1 regulation, such as mitogen-activated protein kinase signaling. A potential role of nuclear receptors in
setting a threshold of AP-1 activity required for the manifestation of a cellular response is discussed (Gritzan, 2002).
The best understood AP-1-dependent process in Drosophila development is a coordinated cell sheet movement known as dorsal closure. During DC, lateral epidermal cells migrate dorsally and close the epidermis on the dorsal side of the embryo. Failure to undergo DC results in a characteristic dorsal open phenotype, the cuticle of affected embryos displays a dorsal hole. Mutations in genes encoding the Drosophila homologs of JNKK, (JNK, Jun and Fos) all give rise to similar dorsal open phenotypes. Thus, it is thought that DC requires activation of Jun/Fos heterodimers by a JNK-type MAPK cascade. Embryos homozygous for kay1, a fos null allele are devoid of zygotic Fos activity and DC fails. A large dorsal hole forms and the cuticle collapses. In an embryo homozygous kay2, a hypomorphic fos-allele, AP-1 activity is reduced but not eliminated. Correspondingly, the DC phenotype is weaker. The embryo displays a small dorso-anterior hole (Gritzan, 2002).
To test whether Drosophila NRs can antagonize AP-1, a variety of AP-1 constructs were in the embryonic epidermis. Interestingly, expression of some, but not all, NRs tested result in DC phenotypes of different strengths. Expression of Svp in the dorsal epidermis under the control of pnrGal4 results in a DC phenotype reminiscent of that of kay2 homozygotes. This finding is consistent with a suppression of AP-1 activity by Svp. Similarly, expression of Tll under the control of a heat shock promoter causes a weak dorsal open phenotype. The differentiation of ventral cells does not seem to be disturbed by Tll expression since the pattern of denticles in this part of the epidermis appears grossly normal. Thus, Tll expression specifically affects the dorsal epidermis where AP-1 activity is required. The expression of Knrl under the control of pnrGal4 elicits stronger DC phenotypes with the dorsal hole frequently extending over several segments (Gritzan, 2002).
Does modulation of AP-1 activity by NRs occur only in situations where AP-1 is regulated by JNK or does this type of regulation also operate in different contexts? A function for Fos downstream of ERK has been demonstrated in the differentiation of wing veins. Extra vein material can result from elevated levels of ERK, as in flies carrying a gain-of-function allele of the rolled gene, which encodes Drosophila ERK. This allele, called rolledSevenmaker (rlSem), encodes a form of ERK with increased resistance to inactivation by dephosphorylation. Expression of a dominant-negative form of Fos in the wings of rlSem flies results in loss of ectopic vein material. Conversely, overexpression of Fos enhances the extra-vein phenotype caused by rlSem. 32B Gal4, UAS Sem flies express the RlSem form of ERK in the wing from a UAS-driven transgene. As a consequence of elevated levels of ERK activity, these animals develop ectopic wing vein material. Reducing fos gene dosage in this system strongly suppresses the vein phenotype, consistent with the proposed role of Fos as an ERK effector. Thus, 32B Gal4 UAS Sem flies provide a suitable system to examine how genetic manipulations of AP-1 activity affect vein differentiation. To investigate a potential role of the Drosophila NRs in this process, one copy of kni, eg, tll or svp was removed in 32B Gal4, UAS Sem flies. Reducing kni function does not influence the vein phenotype. However, heterozygosity for any of the other three receptors tested reproducibly leads to a mild enhancement of the ectopic vein differentiation. As an unambiguously scoreable criterion to statistically evaluate phenotypic effects, the presence of ectopic vein material posterior to L5 was chosen. This area of the wing is relatively resistant to the formation of extra vein material. Quantitative analysis clearly shows that whereas the formation of extra vein material posterior to L5 in 32B Gal4 UAS Sem flies is suppressed by reducing fos activity, it is enhanced by a reduction of eg, svp or tll function. These data suggest that all three NRs antagonize AP-1 activity in wing vein differentiation, conceivably in a redundant manner (Gritzan, 2002).
It is speculated that the modulation of AP-1 activity by NRs contributes to what has recently been termed signal consolidation. Cells have to place a value on incoming signals (e.g. EGF-induced ERK activity) such that they are either answered by a biological response (e.g. the execution of a transcriptional program) or disregarded as noise. It is proposed that the modulation of AP-1 activity by NRs facilitates the interpretation of the EGF signal in wing vein differentiation by defining a threshold of ERK activity. Cells in which ERK activity does not reach this threshold do not mount an AP-1-dependent transcriptional response to the EGF signal. When transrepressional control is impaired (as in the svp, tll double mutant clones) the threshold is lowered and more cells than appropriate interpret EGF-induced ERK activity as a consolidated signal. This leads to the formation of ectopic vein material. This model is supported by the finding that the ectopic vein tissue observed in clones of tll and svp mutant tissue did arise close to the position of the endogenous veins and not randomly throughout the clonal area. Thus, the regulation of AP-1 by NRs appears to convey cell-intrinsic information (Gritzan, 2002).
Chen, Y.-J., et al. (2002). Tramtrack69 is required for the early repression of tailless expression. Mech. Dev. 116: 75-83. 12128207
Cinnamon, E., et al. (2004). Capicua integrates input from two maternal systems in Drosophila
terminal patterning. EMBO J. 23: 4571-4582. 15510215
Cockerill, K.A., Billin, A.N. and Poole, S.J. (1993). Regulation of expression domains and effects of ectopic expression reveal gap gene-like properties of the linked pdm genes of Drosophila. Mech Dev. 41: 139-153
Costa, M., Wilson, E. T. and Wieschaus, E. (1994). A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation. Cell 76 (6): 1075-1089
Daniel, A., Dumstrei, K., Lengyel, J. A. and Hartenstein, V. (1999). The control of cell fate in the embryonic visual system by atonal, tailless and
EGFR signaling. Development 126: 2945-2954.
de las Heras, J. M. and Casanova, J. (2006). Spatially distinct downregulation of Capicua repression and Tailless activation by the Torso RTK pathway in the Drosophila embryo. Mech. Dev. 123(6): 481-6. 16753285
Deshpande, G., Calhoun, G. and Schedl, P. (2004). Overlapping mechanisms function to establish transcriptional quiescence in the embryonic Drosophila germline. Development 131: 1247-1257. 14960492
Diaz, R. J., et al. (1996). Graded effect of tailless on posterior gut development: molecular basis of an allelic series of a nuclear receptor gene. Mec. Dev. 54: 119-130
Firth, L., et al. (2000). Identification of genomic regions that interact with a viable allele
of the Drosophila protein tyrosine phosphatase Corkscrew. Genetics 156: 733-748.
Finley, K. D., et al. (1998). dissatisfaction encodes a Tailless-like nuclear receptor expressed in a subset of CNS
neurons controlling Drosophila sexual behavior. Neuron 21(6): 1363-74.
Furriols, M., Sprenger, F. and Casanova, J. (1996). Variation in the number of activated torso receptors correlates with differential gene expression. Development 122: 2313-7
Gaul, U. and Weigel, D. (1991). Regulation of Kruppel expression in the anlage of the Malpighian tubules in the Drosophila embryo. Mech. Dev. 33: 57-67
Ghiglione, C., Perrimon, N. and Perkins, L. A. (1999). Quantitative variations in the level of MAPK activity control patterning of the embryonic termini in Drosophila. Dev. Biol. 205(1): 181-93.
Goltsev, Y., et al. (2004). Different combinations of gap repressors for common stripes in Anopheles and Drosophila embryos. Dev. Biol. 275: 435-446. 15501229
Goriely, A., et al. (1996). A functional homologue of goosecoid in Drosophila.
Development 122: 1641-1650
Greenwood, S. and Struhl, G. (1997). Different levels of Ras activity can specify distinct
transcriptional and morphological consequences in early Drosophila embryos. Development 124(23): 4879-4886.
Gritzan, U., Weiss, C., Brennecke, J. and Bohmann, D. (2002). Transrepression of AP-1 by nuclear receptors in Drosophila. Mech. Dev. 115: 91-100. 12049770
Gursky, V. V., Jaeger, J., Kozlov, K. N., Reinitz, J. and Samsonov, A. M. (2004). Pattern formation and nuclear divisions are uncoupled in Drosophila segmentation: Comparison of spatially discrete and continuous models. Physica D 197: 286-302. Full text: Gursky, 2004
Gutjahr, T., Frei, E. and Noll, M. (1993). Complex regulation of early paired expression: initial activation by gap genes and pattern modulation by pair-rule genes. Development 117(2): 609-623
Hader, T., et al. (1998). Activation of posterior pair-rule stripe expression in response to maternal caudal and zygotic knirps activities. Mech. Dev. 71(1-2): 177-186.
Haecker, A., et al. (2007). Drosophila brakeless interacts with atrophin and is required for tailless-mediated transcriptional repression in early embryos.
PLoS Biol. 2007 Jun;5(6):e145. PubMed citation: 17503969
Hartmann, B., Reichert, H. and Walldorf, U. (2001). Interaction of gap genes in the Drosophila head: tailless regulates expression of empty spiracles in early embryonic patterning and brain development. Mech. Dev. 109(2): 161-72. 11731230
Hollemann, T., Bellefroid, E. and Pieler, T. (1998). The Xenopus homologue of the Drosophila gene tailless has a function in early eye development. Development 125(13): 2425-2432.
Hou, X.S., Chou, T.B., Melnick, M.B. and Perrimon, N. (1995). The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Cell 81(1): 63-71
Huelskamp, M. and Tautz, D. (1991). Gap genes and gradients--the logic behind the gaps. BioEssays 13: 261-268
Jaeger, J., et al. (2004a). Dynamic control of positional information in the early Drosophila embryo. Nature 430: 368-371. 15254541
Jaeger, J., et al. (2004b). Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster. Genetics 167: 1721-1737. 15342511
Jimenez, G., et al. (2000). Relief of gene repression by torso RTK signaling: role of capicua in Drosophila terminal and
dorsoventral patterning. Genes Dev. 14(2): 224-31.
Kispert, A., Herrmann, B.B., Leptin, M. and Reuter, R. (1994). Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium and Locusta. Genes Dev. 8(18): 2137-50
Klingler, M. and Gergen, J. P. (1993). Regulation of runt transcription by Drosophila
segmentation genes. Mech Dev 43: 3-19
La Rosee, A., et al. (1997). Mechanism and Bicoid-dependent control of hairy stripe 7 expression in the posterior region of the Drosophila embryo. EMBO J. 16(14): 4403-4411.
Leatherman, J. L., Levin, L., Boero, J. and Jongens, J. A. (2002).
germ cell-less acts to repress transcription during the establishment of the Drosophila germ cell lineage. Curr. Biol. 12: 1681-1685. 12361572
Liaw, G. J. and Lengyel, J. A. (1993). Control of tailless expression by bicoid, dorsal and
synergistically interacting terminal system regulatory elements. Mech Dev 40: 47-61
Liaw, G.J., Rudolph, K.M., Huang, J.D., Dubnicoff, T., Courey, A.J. and Lengyel, J. (1995). The torso response element binds GAGA and NTF-1/Elf-1, and regulates tailless by relief of repression. Genes Dev. 9: 3163-3176
Liu, X. and Lengyel. J. A. (2000). Drosophila arc encodes a novel adherens
junction-associated PDZ domain protein
required for wing and eye development. Dev. Biol. 221: 419-434.
Lloyd, T. E., et al. (2002). Hrs regulates endosome membrane invagination and
tyrosine kinase receptor signaling in Drosophila. Cell 108: 261-26. 11832215
Lowe, C. J., et al. (2003). Anteroposterior patterning in hemichordates and the origins of the chordate nervous system. Cell 113: 853-865. 12837244
Margolis, J. S., et al. (1995). Posterior stripe expression of hunchback is driven from
two promoters by a common enhancer element. Development 121: 3067-3077
Mlodzik, M. and Gehring, W.J. (1987) Hierarchy of the genetic interactions that specify the anteroposterior segmentation pattern of the Drosophila embryo as monitored by caudal protein expression. Development 101: 421-435
Mohler, J. (1995). Spatial regulation of segment polarity gene expression in
the anterior terminal region of the Drosophila blastoderm embryo. Mech Dev 50: 151-161
Monaghan, A.P., Grau, E., Boack, D. and Schutz, G.(1995). The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development 121: 839-853
Monaghan, A. P., et al. (1997). Defective limbic system in mice lacking the tailless gene. Nature 390(6659): 515-517.
Much, J. W., et al. (2000). The fax-1 nuclear hormone receptor regulates axon pathfinding and
neurotransmitter expression. Development 127(4): 703-12.
Nakamura, A., Amikura, R., Mukai, M., Kobayashi, S. and Lasko, P. (1996). Requirement for a noncoding RNA in Drosophila polar granules for germ cell establishment. Science 274: 2075-2079. 8953037
Ochoa-Espinosa, A., Yucel, G., Kaplan, L., Pare, A., Pura, N., Oberstein, A.,
Papatsenko, D. and Small S. (2005). The role of binding site cluster strength
in Bicoid-dependent patterning in Drosophila.
Proc. Natl. Acad. Sci. 102(14): 4960-5. 15793007
Parouch, Z., Finley, R.L., Kidd, T., Wainwright, S.M., Ingham, P.W., Brent, R. and Ish-Horowicz, D. (1994). Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell 79(5): 805-815
Paroush, Z., Wainwright, S. M. and Ish-Horowicz, D. (1997). Torso signalling regulates terminal patterning in Drosophila by antagonising Groucho-mediated repression. Development 124(19): 3827-3834.
Perkins, T. J., Jaeger, J., Reinitz, J. and Glass, L. (2006). Reverse engineering the gap gene network of Drosophila melanogaster. PLoS Comput. Biol. 2(5): e51. 16710449
Pignoni, F., Baldarelli, R.M., Steingrimsson, E., Diaz, R.J., Patopoutian, A., Merriam, J.R. and Lengyel, J.A. (1990). The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily. Cell 62: 151-163
Pignoni, F., Steingrimsson, E. and Lengyel, J.A. (1992). bicoid and the terminal system activate tailless expression in the early Drosophila embryo. Development 115: 239-251HREF="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=92347183&dopt=Abstract">
Qian, S., Capovilla, M. and Pirrotta, Vl. (1993). Molecular mechanisms of pattern formatin by the BRE enhancer of the Ubx gene. EMBO J. 12(10): 3865-3877
Reinitz, J. and Levine, M. (1990). Control of the initiation of homeotic gene expression by the gap genes giant and tailless in Drosophila. Dev. Biol. 140: 57-72
Rivera-Pomar, R. and Jäckle, H. (1996). From gradients to stripes in Drosophila embryogenesis: Filling in the gaps. Trends Genet 12: 478-483. 8973159
Rudolph, K. M., et al. (1997). Complex regulatory region mediating tailless expression in early embryonic patterning and brain development. Development 124(21): 4297-4308.
Sanchez, L. and Thieffry, D. (2001). A logical analysis of the gap gene system. J. Theor. Biol. 211: 115-141. 11419955
Schroder, R., et al. (2000). Conserved and divergent aspects of terminal patterning in the beetle Tribolium castaneum. Proc. Natl. Acad. Sci. 97: 6591-6596.
Seydoux, G. and Dunn, M. A. (1997). Transcriptionally repressed germ cells lack a subpopulation of phosphorylated RNA polymerase II in early embryos of Caenorhabditis elegans and Drosophila melanogaster. Development 124: 2191-2201. 9187145
Sluder, A. E., Lindbloom, T. and Ruvkun, G. (1997). The Caenorhabditis elegans orphan nuclear hormone receptor gene rhr-2 functions in early embryonic development. Dev. Biol. 184: 303-319
Stevens, L. M., et al. (2003). The Drosophila embryonic patterning determinant Torsolike is a component of the eggshell. Curr. Biol. 13: 1058-1063. 12814553
Tsai, C. C., Kramer, S. G. and Gergen, J. P. (1998). Pair-rule gene runt restricts orthodenticle expression to the presumptive head of the Drosophila embryo. Dev. Genet. 23(1): 35-44.
Tsuda, L., Inoue, Y.H., Yoo, M.A., Mizuno, M., Hata, M., Lim, Y.M., Adachi, T., Ryo, H., Masamune, Y. and Nishida, Y. (1993). A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila. Cell 72(3): 407-414
Tuckfield, A., et al. (2002). Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors. Mol. Cell. Biol. 22: 1936-1946. 11865070
Urbach, R. and Technau, G. M. (2003). Molecular markers for identified neuroblasts in the developing brain of Drosophila. Development 130: 3621-3637. 12835380
Van Doren, M., Williamson, A. L. and Lehmann, R. (1998). Regulation of zygotic gene expression in Drosophila primordial germ cells. Curr. Biol. 8: 243-246. 9501989
Wang, L. and Coulter, D. E. (1996). bowel, an odd-skipped homolog, functions in the terminal pathway during Drosophila embryogenesis. EMBO J. 15: 3182-3196. 8670819
Wang, L., et al. (2006). Histone deacetylase-associating Atrophin proteins are nuclear receptor corepressors. Genes Dev. 20: 525-530. 16481466
Wimmer, E. A., et al., (1995). Trans- and cis-acting requirements for blastodermal expression of the head gap gene buttonhead. Mech. Dev. 53: 235-245
Wu, L. H. and Lengyel, J. A. (1998). Role of caudal in hindgut specification and gastrulation suggests homology between Drosophila amnioproctodeal invagination and vertebrate blastopore. Development 125: 2433-2442.
Yip, M.L, Lamka, M. L. and Lipshitz, H. D. (1997). Control of germ-band retraction in Drosophila by the zinc-finger protein HINDSIGHT. Development 124 (11): 2129-2141.
Younossi-Hartenstein, A., et al. (1997). Control of early neurogenesis in the Drosophila brain by the head gap genes tll, otd, ems, and btd. Dev. Biol 182: 270-283
Yu, R. T., et al. (1994). Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature 370: 375-379
Yu, R. T., et al. (2000). The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proc. Natl. Acad. Sci. 97: 2621-2625.
Zhang, C. L., Zou. Y., Yu, R. T., Gage, F. H. and Evans, R. M. (2006). Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1. Genes Dev. 20: 1308-1320. PubMed citation; Online text
date revised: 10 April 2008
Home page: The Interactive Fly © 1997 Thomas B. Brody, Ph.D.
The Interactive Fly resides on the
Society for Developmental Biology's Web server.