Gene name - pannier
Synonyms - dGATAa
Cytological map position - 89B9-10
Function - transcription factor
Symbol - pnr
Genetic map position - 3-58
Classification - zinc finger
Cellular location - nuclear
Kim, A. R., Choi, E. B., Kim, M. Y. and Choi, K. W. (2017). Angiotensin-converting enzyme Ance is cooperatively regulated by Mad and Pannier in Drosophila imaginal discs. Sci Rep 7(1): 13174. PubMed ID: 29030610
Angiotensin-converting enzyme (ACE) is an evolutionarily conserved peptidyl dipeptidase. Mammalian ACE converts angiotensin I to the active vasoconstrictor angiotensin II, thus playing a critical role for homeostasis of the renin-angiotensin system. In Drosophila, the ACE homolog Ance is expressed in specific regions of developing organs, but its regulatory mechanism has not been identified. This study provides evidence that Ance expression is regulated by a combination of Mad and Pannier (Pnr) in imaginal discs. Ance expression in eye and wing discs depends on Dpp signaling. The Mad binding site of Ance regulatory region is essential for Ance expression. Ance expression in imaginal discs is also regulated by the GATA family transcription factor Pnr. Pnr directly regulates Ance expression by binding to a GATA site of Ance enhancer. In addition, Pnr and Mad physically and genetically interact. Ance null mutants are morphologically normal but show genetic interaction with dpp mutants. Furthermore, human SMAD2 and GATA4 were shown to physically interact, and ACE expression in HEK293 cells is regulated by SMAD2 and GATA4. Taken together, this study reveals a cooperative mechanism of Ance regulation by Mad and Pnr. The data also suggest a conserved transcriptional regulation of human ACE.
|Immarigeon, C., Bernat-Fabre, S., Auge, B., Faucher, C., Gobert, V., Haenlin, M., Waltzer, L., Payet, A., Cribbs, D. L., Bourbon, H. G. and Boube, M. (2019). Drosophila Mediator subunit Med1 is required for GATA-dependent developmental processes: divergent binding interfaces for conserved coactivator functions. Mol Cell Biol. PubMed ID: 30670567
DNA-bound transcription factors (TFs) governing developmental gene regulation have been proposed to recruit Polymerase II machinery at gene promoters through specific interactions with dedicated subunits of the evolutionarily-conserved Mediator complex (MED). However, whether such MED subunit specific functions and partnerships have been conserved during evolution has been poorly investigated. To address this issue, the first Drosophila loss-of-function mutants were generated for Med1, known as a specific cofactor for GATA TFs and hormone nuclear receptors in mammals. Med1 was shown to be required for cell proliferation, and hematopoietic differentiation depending on the GATA TF Serpent (Srp). Med1 binds Srp in cultured cells and in vitro through its conserved GATA Zinc Finger DNA-binding domain and the divergent Med1 C-terminal. Interestingly, GATA/Srp interaction occurs through the longest Med1 isoform, suggesting a functional diversity of MED complex populations. Furthermore, it was shown that Med1 acts as a coactivator for the GATA factor Pannier during thoracic development. In conclusion, the Med1 requirement for GATA-dependent regulatory processes is a common feature in insects and mammals, although binding interfaces have diverged. Further work in Drosophila should bring valuable insights to fully understand GATA-MED functional partnerships, which probably involve other MED subunits depending on the cellular context.
|Immarigeon, C., et al. (2019). Drosophila mediator aubunit Med1 is required for GATA-dependent developmental processes: Divergent binding interfaces for conserved coactivator functions. Mol Cell Biol 39(7). PubMed ID: 30670567
DNA-bound transcription factors (TFs) governing developmental gene regulation have been proposed to recruit polymerase II machinery at gene promoters through specific interactions with dedicated subunits of the evolutionarily conserved Mediator (MED) complex. However, whether such MED subunit-specific functions and partnerships have been conserved during evolution has been poorly investigated. To address this issue, this study generated the first Drosophila melanogaster loss-of-function mutants for Med1, known as a specific cofactor for GATA TFs and hormone nuclear receptors in mammals. Med1 was shown to be required for cell proliferation and hematopoietic differentiation depending on the GATA TF Serpent (Srp). Med1 physically binds Srp in cultured cells and in vitro through its conserved GATA zinc finger DNA-binding domain and the divergent Med1 C terminus. Interestingly, GATA-Srp interaction occurs through the longest Med1 isoform, suggesting a functional diversity of MED complex populations. Furthermore, Med1 was shown to act as a coactivator for the GATA factor Pannier during thoracic development. In conclusion, the Med1 requirement for GATA-dependent regulatory processes is a common feature in insects and mammals, although binding interfaces have diverged. Further work in Drosophila should bring valuable insights to fully understand GATA-MED functional partnerships, which probably involve other MED subunits depending on the cellular context.
There are three GATA homologs in Drosophila: Serpent (dGATAb), found in the midgut and ovary (Lossky, 1995), Pannier (GATA-2), found in the dorsal epidermis, and dGATAc, found in the procephalic [Image] region, posterior spiracles, gut, and central nervous system.
Pannier acts as a local repressor of achaete and scute and is required for the normal pattern of sensory bristles in those parts of the epithelium where it is expressed. pannier mutation may take one of two forms: either an over- or under-expression of achaete-scute. Consequently the phenotype shows either an overabundance or a lack of bristles.
Studies suggest that Pannier's action on achaete-scute is negative. In this view, mutants with too few bristles would be due to a hyperactive enzyme, resulting in accentuated repressive activity. These mutations are dominant, affecting the primary structure of Pannier and suggest that mutant Pannier protein acts as a non-functional heterodimer with another transcription factor (Ramain, 1993).
Two other proteins act as repressors of achaete-scute: hairy and extramachrochaete. Loss of these two functions also results in overexpression of achaete-scute and ectopic bristles.
To identify genes involved in the patterning of adult structures, Gal4-UAS (upstream activating site) technology was used to visualize patterns of gene expression directly in living flies. The gene yellow (y) was made sensitive to Gal4 control and a Gal4-containing P element was inserted randomly into the fly genome. A large number of Gal4 insertion lines were generated and their expression patterns studied. In addition to identifying several characterized developmental genes, the approach revealed previously unsuspected genetic subdivisions of the thorax, which may control the disposition of pattern elements. For example, the pannier expression domain marks a dorsal band along the length of the body, from the occipital head region to the end of the abdomen but excluding the terminalia. In the notum (derived from the wing imaginal disc), the gene labels a territory extending from the dorsal midline laterally to a longitudinal (anterior to posterior) straight line defined by the dorsocentral bristles. Another insertion em462 shows y+ rescue in a territory adjacent to the pannier domain; it is also demarcated medially by the position of the dorsocentral bristles. The em462 domain extends laterally but does not reach the more lateral region of the notum. Possibly, the gene iroquois defines a distinct, more lateral domain.
The subdivision of the notum demarcated by the dorsocentral bristles may be significant because this same line also appears to demarcate the most medial expression border of the wingless gene. In the notum, wingless is expressed in a narrow stripe and the wingless domain is included within the em462 domain, extending laterally from the dorsocentral bristles. Apparently there is no overlap between pnr and wg in the scutum (the anterior part of the notum), but they do overlap in the more posterior scutellum. Genetic interaction experiments show that pannier acts as a negative regulator of wingless in the notum and suggest that some of the effects of pannier mutants are produced through an alteration of wingless function. Interestingly, the dorsocentral line is known not to function as a cell lineage border. In addition to bristles, another frequent pattern element in insects is pigmentation, often disposed in longitudial bands and used as a diagnostic criterion for the taxonomy of dipteran species. The medial boundary of a diagnostic pigment band is exactly delimited by the same longitudinal line straddling the dorsocentral bristles that in the Drosophila demarcates pannier, wingless and em462 (Calleja, 1996).
The pannier gene of Drosophila encodes a zinc-finger transcription factor of the GATA family and is involved in several developmental processes during embryonic and imaginal development. Novel aspects of the regulation and function of pnr during embryogenesis are reported in this study. Previous work has shown that pnr is activated by decapentaplegic (dpp) in early development, but it has been found that after stage 10, the roles are reversed and pnr becomes an upstream regulator of dpp. This function of pnr is necessary for the activation of the Dpp pathway in the epidermal cells implicated in dorsal closure and is not mediated by the JNK pathway, which is also necessary for Dpp activity in these cells. In addition, pnr behaves as a selector-like gene in generating morphological diversity in the dorsoventral body axis. It is responsible for maintaining a subdivision of the dorsal half of the embryo into two distinct, dorsomedial and dorsolateral, regions, and also specifies the identity of the dorsomedial region. These results, together with prior work on its function in adults, suggest that pnr is a major factor in the genetic subdivision of the body of Drosophila (Herranz, 2001).
In early development, pnr is activated in response to dpp activity in a broad dorsal domain, which extends from parasegments 2/3 to the border between 13/14, although the borders are not strictly parasegmental. The control by dpp is consistent with the effect of brk mutations on early pnr expression. The original expression domain is substantially modified during embryogenesis. By germ band extension (stage 10) pnr activity is limited dorsally by the border between the epidermis and the amnioserosa, and laterally by the dorsal border of iro. It is not known which factor(s) is responsible for the loss of expression in the amnioserosa, although likely candidates are several genes specifically active in this region, such as Race, zen, hindsight or serpent. In addition, it is not known how the late expression is regulated at the lateral border. It is not achieved by iro, since the loss of the entire Iroquois complex does not affect pnr expression (Herranz, 2001).
Another modification occurs between stages 10 and 11, and is the loss of expression in the A8 segment. Expectedly, it is under the control of Abd-B; in Abd-B mutants the gap in A8 does not appear. However, none of the known Abd-B target genes (sal, ems and grn) is involved in the regulation, since their mutations do not affect pnr expression. The finding that lin, which is considered as a co-factor of Abd-B, is involved, suggests that downregulation of pnr in the A8 segment is mediated either by an unknown Abd-B target or directly by interaction between the Abd-B and Lin products. It is not clear why pnr activity has to be eliminated precisely in the A8 segment. This segment gives rise to the spiracles, protruding structures that are very different from those differentiated by the other abdominal segments where pnr remains active. In fact, there are several Abd-B target genes specifically activated in the spiracles. It is possible that the formation of these structures demands that the pnr activity, which specifies larval epidermis of very different morphology, be turned off (Herranz, 2001).
Interestingly, whereas early pnr expression is under dpp control, the late expression is not. Late inactivation of the Dpp pathway, using a dominant negative form of thick veins, does not modify pnr expression. In addition, mutations at brk, which allow higher response levels to Dpp signaling fail to affect pnr expression in late development, although they affect early expression. This indicates that pnr expression is controlled independently in early and late development, and by different factors (Herranz, 2001).
There is already evidence that pnr has distinct functions during embryogenesis. Its activity in the dorsal epidermis is required for dorsal closure and it is also expressed in the dorsal mesoderm where it is involved in the specification of cardiac cells. Evidence is provided for another and more general function of pnr; it specifies the identity of a dorsomedial body region that spans from the labial segment to the end of the abdomen. This is clearly demonstrated by the effects seen in mutant embryos and after ectopic expression experiments. In pnrVX6 embryos, the dorsomedial cuticle does not form, and there is an expansion of the dorsolateral epidermis, suggesting that the cells of the dorsomedial domain acquire a dorsolateral fate. The ectopic expression experiments also point to the same conclusion. In larvae ectopically expressing pnr (arm-Gal4/UAS-pnr) the entire larval epidermis acquires dorsomedial features, whereas using more restricted drivers (Ubx-Gal4, wg-Gal4) the transformation is limited to the region where the Pnr protein is present, suggesting that the effect of pnr is cell autonomous. Thus, the Pnr protein is able by itself to trigger a developmental pathway, a typical property of selector gene products. In addition, it induces a ventral to dorsal transformation, corresponding to each segment, indicating that it acts in combination with Hox genes. These observations indicate that selector genes in the AP and DV axes have to co-operate to determine the different spatial patterns (Herranz, 2001).
The transformation of ventral and dorsolateral epidermis towards dorsomedial observed after ectopic pnr expression is also reflected in the activity of marker genes of the distinct regions. Characteristic genes of the ventral neuroectoderm such as BP102 for the CNS or buttonhead are suppressed. In addition, pnr is able to suppress iro activity, a property that, as in the adult cells, is important to keep the dorsomedial and dorsolateral domains separate during embryogenesis (Herranz, 2001).
The developmental effects observed after either the loss or gain of pnr function in the larval epidermis resemble those reported for the adult cuticle. In the latter, it has been shown that the activity of pnr maintains the segregation of the dorsal cuticle into medial and lateral domains, and also specifies the identity of a medial domain. This indicates that pnr has a general function involved in the subdivision of the body along the DV axis. The longitudinal stripe of pnr expression established during embryogenesis is probably a major constituent of the body and represents a zone of common identity (Herranz, 2001).
In addition, Pnr has other more concrete functions connected with the specification of cardiac cells and embryonic dorsal closure. The involvement of pnr in dorsal closure is exerted through its activation of dpp in late embryogenesis, which is responsible for the formation of the Dpp stripe at the junction of the epidermis with the amnioserosa. Normal functioning of the Dpp pathway in this region is required for dorsal closure, suggesting that defects in dorsal closure observed in pnr mutant embryos is the result of the lack of the dorsal dpp stripe (Heranz, 2001).
There is evidence that this dpp expression requires function of the JNK kinase pathway, and it also requires pnr activity. The observation that in the absence of pnr activity the expression of puc, the end element of the JNK pathway is normal, indicates that in pnr mutants the JNK pathway is normally active. In turn, it shows that the activation of dpp in the dorsal stripe requires independent inputs from both the JNK pathway and pnr (Herranz, 2001).
One intriguing aspect of pnr function is that it is able to induce a developmental modification in all ectodermal structures along the DV body axis except in the amnioserosa, the most dorsal tissue. Even under conditions in which pnr is transcribed and translated in all the amnioserosa cells, it does not appear to elicit any developmental effect; none of the amnioserosa marker genes is affected by forcing pnr activity and the retraction of the germ band [a morphological indicator of the function of specific amnioserosa genes is also normal. Similarly, pnr is able to induce dpp activity all over the body except in the amnioserosa, where the presence of the Pnr protein appears to be inconsequential. This situation resembles the phenotypic suppression/posterior prevalence phenomenon discovered in the Hox genes specifying the AP body axis. It consists of a functional inactivation of a Hox protein by the presence of another normally expressed in a more posterior region of the body. It is conceivable that there might be a dorsal prevalence in the DV axis, by which dorsal expressing genes are functionally dominant over the ventral expressing ones. It would be expected that genes specifying amnioserosa would be able to transform all structures since they would be ranking highest in the functional hierarchy (Herranz, 2001).
Axial patterning is crucial for organogenesis. During Drosophila eye development, dorso-ventral (DV) axis determination is the first lineage restriction event. The eye primordium begins with a default ventral fate, on which the dorsal eye fate is established by expression of the GATA-1 transcription factor pannier (pnr). Earlier, it was suggested that loss of pnr function induces enlargement in the dorsal eye due to ectopic equator formation. Interestingly, this study found that in addition to regulating DV patterning, pnr suppresses the eye fate by downregulating the core retinal determination genes eyes absent (eya), sine oculis (so) and dacshund (dac) to define the dorsal eye margin. pnr acts downstream of Ey and affects the retinal determination pathway by suppressing eya. Further analysis of the 'eye suppression' function of pnr revealed that this function is likely mediated through suppression of the homeotic gene teashirt (tsh) and is independent of homothorax (hth), a negative regulator of eye development. Pnr expression is restricted to the peripodial membrane on the dorsal eye margin, which gives rise to head structures around the eye, and pnr is not expressed in the eye disc proper that forms the retina. Thus, pnr has dual function, during early developmental stages pnr is involved in axial patterning whereas later it promotes the head specific fate. These studies will help in understanding the developmental regulation of boundary formation of the eye field on the dorsal eye margin (Oros, 2011).
This study has addressed a basic question pertaining to regulation of patterning, growth and differentiation of the developing eye field. The results provide an important insight into the role of pnr, a gene known to confer dorsal eye identity during axial patterning of the eye. The onset of pnr expression during early eye development results in the generation of dorsal lineage in the eye. It results in the formation of a DV boundary (equator), which triggers N signaling at the border of the dorsal and ventral compartments to initiate growth and differentiation (Oros, 2011).
The spatial as well as temporal requirement for the genes controlling ventral eye growth and development have been tested. During early eye development, prior to the onset of pnr expression in the dorsal eye, entire early eye primordium is ventral in fate. Removal of function of genes controlling ventral eye development prior to the onset of pnr expression results in complete elimination of the eye field whereas later when pnr starts expressing, the eye suppression phenotype gets restricted only to the ventral eye . These studies suggested that pnr plays an important role in dorso-ventral (axial) patterning. However, the role of dorsal selector pnr in retinal determination was unknown (Oros, 2011).
Loss-of-function clones of pnr in the dorsal eye exhibit eye enlargement. It was suggested that when pnr function is abolished in the dorsal eye using loss-of-function clones, it results in the change of dorsal eye fate to ventral. This results in generation of a de novo equator, the border between dorsal and ventral half of the eye, which triggers ectopic N signaling to promote growth and cell proliferation. The same premise has been used to explain the gain-of-function phenotype of pnr in the eye. Misexpression of pnr in the entire eye (ey > pnrD4) generates a completely dorsalized eye field as pnr acts as the dorsal fate selector. The fully dorsalized eye lacks DV polarity (equator), resulting in the complete loss of eye field due to lack of N upregulation. This study addressed another possibility, to see if pnr suppresses the eye fate upon misexpression in the entire eye as evident from the 'no-eye' phenotype (Oros, 2011).
To test if pnr suppresses the eye fate, pnr was misexpressed both in the dorsal and ventral (DV) eye margins of the eye using a bi-Gal4 driver (bi > pnrD4). The rationale was if pnr is only required to assign the dorsal eye fate, in that case pnr misexpression (bi > pnrD4) will assign a dorsal fate on the margin of ventral eye. Thus, by this logic, it would result in generation of a de novo equator on the ventral eye margin, which should manifest as eye enlargements in the ventral eye. The argument was based on the similar premise that was employed to explain that loss-of-function clones of pnr in the dorsal eye generated a new equator and led to the dorsal eye enlargement. No ventral eye enlargements were observed in bi > pnrD4 eye disc. Instead suppression of the eye was seen on both the dorsal as well as ventral margins. The suppression of eye fate on both the dorsal and the ventral margins suggests that pnr, irrespective of the domain where it is expressed, can suppress the eye fate (Oros, 2011).
Since pnr suppresses the eye fate, it is possible that it may be involved in regulation of expression of genes of the core retinal determination (RD) machinery. Loss-of-function of pnr in the dorsal eye clones results in the eye enlargements as evident from Elav positive cells but it does not induce ectopic Ey. Ey expression evolves during eye development and is localized anterior to the morphogenetic furrow in retinal precursor cells and is downregulated and degraded posterior to the furrow in differentiation retinal neurons. In the loss-of-function clones of pnr in the eye, the expression of retinal determination pathway members like Eya, So and Dac, which act downstream to Ey, are ectopically induced. In the converse situation, where pnr was misexpressed on both dorsal and ventral eye margins (bi > pnrD4), ectopic induction of Ey was observed on both the dorsal and the ventral margins whereas the expression of Eya, So and Dac were suppressed. Thus, misexpression of pnr in the eye prevents the photoreceptor differentiation irrespective of the dorsal or ventral domain. Based on these results it is proposed that pnr suppresses the eye fate on the dorsal eye margin by downregulating RD genes like eya, so and dac (Oros, 2011).
Pnr suppresses the eye fate by downregulating tsh which results in suppression of retinal determination genes at the dorsal eye margin. GATA-1 transcription factor pnr, which is expressed in the peripodial membrane (PM) at the dorsal eye margin, suppresses the retinal determination. The suppression of retinal determination genes by pnr can be mediated by two possible ways: (1) pnr directly suppresses the retinal determination genes to suppress the eye. pnr may act downstream to ey and suppress the downstream retinal determination target eya and other downstream genes so and dac. During eye development, ey is required for eye specification and other downstream targets are required for retinal determination. These studies suggest that pnr acts on retinal determination process, which corresponds to the onset of pnr expression in the eye. (2) Alternatively, pnr suppresses the eye by downregulating homeotic gene teashirt (tsh) in the dorsal eye. Interestingly, the tsh gain-of-function in the dorsal eye is complementary to the loss-of-function of pnr in the dorsal eye. tsh is known to act upstream of eya, so and dac. Thus, the dorsal eye enlargement observed in pnr mutant is due to ectopic induction of tsh in the dorsal eye, which in turn can induce the RD genes. Lastly, Pnr mediated suppression of the eye fate is independent of Meis class of homeotic gene, homothorax (hth) function (Oros, 2011).
Since ey is responsible for the specification of the eye field and marks the retinal precursor cells, it suggests that pnr does not affect the eye field formation or specification. In fact pnr affects expression of RD genes eya, so and dac. These results suggest that pnr suppress retinal determination genes. Since endogenous expression of pnr is restricted to the peripodial membrane of the dorsal eye margin, it suggests that pnr may be involved in suppression of retinal determination on the dorsal peripodial membrane. Thus, the results suggest that pnr generally acts at the stage when photoreceptor differentiation is initiated with the formation of the morphogenetic furrow (MF) and promotes the dorsal head cuticle fate by suppressing retinal differentiation (Oros, 2011).
Based on these new findings, it is proposed that pnr may be required for two different functions during eye development: (1) axis determination during DV patterning and (2) suppression of the retinal determination process to define the dorsal eye field margin. These functions of pnr appear to be temporally controlled as DV axis determination takes place in late first- or early second- instar of eye development while suppression of the eye fate is evident in late second instar of larval development (Oros, 2011).
The axis determination function of pnr is required in the earlier time window. This is further validated by the loss-of-function clones of pnr of first category, which are bigger and exhibits non-autonomous dorsal eye enlargement phenotypes. These dorsal eye enlargements that are spanning both wild-type and pnr mutant cells in the eye disc conforms to the notion that when pnr is lost in a group of cells during early development, it fails to confer dorsal identity over the default ventral state. As a consequence de novo equator is generated which results in the ectopic dorsal eye enlargements. Since these clones are always bigger, suggesting that they might be formed earlier. The late function of pnr in suppression of retinal determination is validated both by the gain-of-function studies as well as the loss-of-function clones of second category, which are both bigger as well as smaller in size and are autonomous in nature. These clones have ectopic dorsal eyes, which are restricted within the clones, thereby suggesting that absence of pnr function promotes ectopic eye formation in the dorsal eye margin. Thus, during the early second instar of development, before the onset of retinal differentiation, pnr is required for defining the dorsal lineage by inducing Wg and members of the Iro-C complex. However, later during the late second-instar stage of eye development, when the morphogenetic furrow (MF) is initiated, pnr suppresses the photoreceptor differentiation at the dorsal eye margin. The endogenous expression of pnr in only the peripodial membrane of the dorsal eye margin further confirms this notion. Lack of phenotypes in pnr clones which are restricted to the disc proper (DP) alone verifies pnr localization. Thus, pnr defines the boundary between the eye field and the head cuticle on the dorsal margin. An interesting question will be to identify which gene is responsible for defining the ventral eye margin. In the ventral eye where pnr is not expressed, hth is known to suppress the eye fate. There is a strong possibility that hth may be involved in defining the boundary of eye field on the ventral eye margin between the disc proper and peripodial membrane (Oros, 2011).
Since pnr induces Wg, it is expected that pnr may suppress the eye by induction of Wg. Even though Wg signaling is responsible for suppression of photoreceptor differentiation on both dorsal and ventral eye margins, its regulation is different on both dorsal and ventral eye margins. In the ventral eye, wg is involved in a feedback loop with hth to suppress the eye fate. In the dorsal eye, Pnr induces Wg signaling, which in turn induces the members of Iro-C complex, and ultimately these signaling interactions define the dorsal eye fate. Interestingly, it seems Pnr is not the sole regulator of Wg in the dorsal eye. Since loss-of-function of hth does not exhibit phenotypes similar to the loss-of-function of pnr, it is expected that the positive feedback loop regulation of wg and hth as seen in the ventral eye margin does not hold true on the dorsal eye margin. This study found that hth is not affected in the pnr clones that exhibit dorsal eye enlargements. Furthermore, when clones of hth were made in pnr heterozygous condition, no dorsal eye enlargements were seen suggesting that hth and pnr do not interact. Thus the results also verified that hth is not involved in pnr mediated eye suppression on the dorsal eye margin (Oros, 2011).
It is known that the gain of function of tsh in the dorsal eye results in ectopic eye enlargement whereas gain of function of tsh in the ventral eye result in suppression of ventral eye. The dorsal eye enlargements seen in tsh gain-of-function is a phenotype similar to pnr loss-of-function in the dorsal eye. In pnr loss-of-function clones, it was found that tsh was ectopically induced. Furthermore, when pnr loss-of-function clones were generated in a heterozygous background of the tsh null allele tsh8/CyO, the dorsal eye enlargement phenotype was dramatically suppressed and no longer observed. Interestingly, this study found that dorsal enlargements were there but were not accompanied with ectopic eyes as evident from absence of Elav expression. All these dorsal enlargements were showing strong Ey expression. Among 500 flies counted only two flies were found that showed subtle dorsal eye enlargements. Interestingly, it was also found that in pnr loss-of-function clones the mini-white reporter gene under tsh was ectopically induced. The loss-of-function phenotypes of pnr were more pronounced when tsh was misexpressed in the clones. Thus, pnr expressed in the dorsal peripodial membrane may suppress tsh in the dorsal eye to suppress the eye fate. Interestingly, tsh is known to act upstream of eya, so and dac. Thus, the dorsal eye enlargement observed in the pnr mutant is due to ectopic induction of tsh in the dorsal eye, which in turn can induce the RD genes (Oros, 2011).
The Drosophila eye is similar to the vertebrate eye in several features: (1) the morphogenetic furrow in the fly eye is analogous to the wave of neurogenesis in the vertebrate eye, (2) As in Drosophila, in higher vertebrates dorsal eye genes like Bmp4 and Tbx5 act as 'dorsal selectors' and restrict the expression of ventral eye genes Vax2 and Pax2. These DV expression domains or developmental compartments lead to formation of DV lineage restriction as seen in the Drosophila eye, (3) The DV lineage in the vertebrate eye also develops from a ventral-equivalent initial state. The dorsal genes pnr and iro-C are highly conserved across the species, and are involved in organogenesis and neural development. Therefore, it would be interesting to see whether the dorsal selectors in the vertebrate eye play a role in defining the boundary of the eye by suppressing retinal differentiation (Oros, 2011).
Bases in 5' UTR - 689
Exons - four
Bases in 3'UTR - 688
Pannier has two zinc fingers, a polyglutamine stretch and two helicies rich in hydrophobic amino acids (Ramain, 1993 and Winick, 1993).
date revised: 20 December 99
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