scholarly journals Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent

Development ◽  
2000 ◽  
Vol 127 (6) ◽  
pp. 1325-1336 ◽  
Author(s):  
J. Curtiss ◽  
M. Mlodzik
Keyword(s):  
Eye Development ◽  
Loss Of Function ◽  
Morphogenetic Furrow ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Functional Relationships ◽  
Eye Disc ◽  
Additional Control ◽  
Redundant Functions ◽  
Signaling Components

The Drosophila signaling factor decapentaplegic (dpp) mediates the effects of hedgehog (hh) in tissue patterning by regulating the expression of tissue-specific genes. In the eye disc, the transcription factors eyeless (ey), eyes absent (eya), sine oculis (so) and dachshund (dac) participate with these signaling molecules in a complex regulatory network that results in the initiation of eye development. Our analysis of functional relationships in the early eye disc indicates that hh and dpp play no role in regulating ey, but are required for eya, so and dac expression. We show that restoring expression of eya in loss-of-function dpp mutant backgrounds is sufficient to induce so and dac expression and to rescue eye development. Thus, once expressed, eya can carry out its functions in the absence of dpp. These experiments indicate that dpp functions downstream of or in parallel with ey, but upstream of eya, so and dac. Additional control is provided by a feedback loop that maintains expression of eya and so and includes dpp. The fact that exogenous overexpression of ey, eya, so and dac interferes with wild-type eye development demonstrates the importance of such a complicated mechanism for maintaining proper levels of these factors during early eye development. Whereas initiation of eye development fails in either Hh or Dpp signaling mutants, the subsequent progression of the morphogenetic furrow is only slowed down. However, we find that clones that are simultaneously mutant for Hh and Dpp signaling components completely block furrow progression and eye differentiation, suggesting that Hh and Dpp serve partially redundant functions in this process. Interestingly, furrow-associated expression of eya, so and dac is not affected by double mutant tissue, suggesting that some other factor(s) regulates their expression during furrow progression.

Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2181-2191 ◽  
Author(s):  
G. Halder ◽  
P. Callaerts ◽  
S. Flister ◽  
U. Walldorf ◽  
U. Kloter ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Compound Eye ◽  
Eye Development ◽  
Positive Feedback Loop ◽  
Eyes Absent ◽  
Regulatory Interactions ◽  
Sine Oculis ◽  
Eye Disc ◽  
Embryonic Head ◽  
Genetic Hierarchy

The Drosophila Pax-6 gene eyeless acts high up in the genetic hierarchy involved in compound eye development and can direct the formation of extra eyes in ectopic locations. Here we identify sine oculis and eyes absent as two mediators of the eye-inducing activity of eyeless. We show that eyeless induces and requires the expression of both genes independently during extra eye development. During normal eye development, eyeless is expressed earlier than and is required for the expression of sine oculis and eyes absent, but not vice versa. Based on the results presented here and those of others, we propose a model in which eyeless induces the initial expression of both sine oculis and eyes absent in the eye disc. sine oculis and eyes absent then appear to participate in a positive feedback loop that regulates the expression of all three genes. In contrast to the regulatory interactions that occur in the developing eye disc, we also show that in the embryonic head, sine oculis acts in parallel to eyeless and twin of eyeless, a second Pax-6 gene from Drosophila. Recent studies in vertebrate systems indicate that the epistatic relationships among the corresponding vertebrate homologs are very similar to those observed in Drosophila.

Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1731-1745 ◽  
Author(s):  
A.L. Kolodkin ◽  
A.T. Pickup ◽  
D.M. Lin ◽  
C.S. Goodman ◽  
U. Banerjee
Keyword(s):  
Genetic Background ◽  
Egf Receptor ◽  
Transmembrane Domain ◽  
Loss Of Function ◽  
Morphogenetic Furrow ◽  
Eye Disc ◽  
Son Of Sevenless ◽  
Photoreceptor Development ◽  
Star Gene

Loss-of-function mutations in Star impart a dominant rough eye phenotype and, when homozygous, are embryonic lethal with ventrolateral cuticular defects. We have cloned the Star gene and show that it encodes a novel protein with a putative transmembrane domain. Star transcript is expressed in a dynamic pattern in the embryo including in cells of the ventral midline. In the larval eye disc, Star is expressed first at the morphogenetic furrow, then in the developing R2, R5, and R8 cells as well as in the posterior clusters of the disc in additional R cells. Star interacts with Drosophila EGF receptor in the eye and mosaic analysis of Star in the larval eye disc reveals that homozygous Star patches contain no developing R cells. Taken together with the expression pattern at the morphogenetic furrow, these results demonstrate an early role for Star in photoreceptor development. Additionally, loss-of-function mutations in Star act as suppressors of R7 development in a sensitized genetic background involving the Son of sevenless (Sos) locus, and overexpression of Star enhances R7 development in this genetic background. Based on the genetic interactions with Sos, we suggest that Star also has a later role in photoreceptor development including the recruitment of the R7 cell through the sevenless pathway.

Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2253-2260 ◽  
Author(s):  
T. Niimi ◽  
M. Seimiya ◽  
U. Kloter ◽  
S. Flister ◽  
W.J. Gehring
Keyword(s):  
Target Genes ◽  
Ectopic Expression ◽  
Direct Interaction ◽  
Loss Of Function ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Eye Morphogenesis

The Pax-6 gene encodes a transcription factor with two DNA-binding domains, a paired and a homeodomain, and is expressed during eye morphogenesis and development of the nervous system. Pax-6 homologs have been isolated from a wide variety of organisms ranging from flatworms to humans. Since loss-of-function mutants in insects and mammals lead to an eyeless phenotype and Pax-6 orthologs from distantly related species are capable of inducing ectopic eyes in Drosophila, we have proposed that Pax-6 is a universal master control gene for eye morphogenesis. To determine the extent of evolutionary conservation of the eye morphogenetic pathway, we have begun to identify subordinate target genes of Pax-6. Previously we have shown that expression of two genes, sine oculis (so) and eyes absent (eya), is induced by eyeless (ey), the Pax-6 homolog of Drosophila. Here we present evidence from ectopic expression studies in transgenic flies, from transcription activation studies in yeast, and from gel shift assays in vitro that the EY protein activates transcription of sine oculis by direct interaction with an eye-specific enhancer in the long intron of the so gene.

Differential interactions ofeyelessandtwin of eyelesswith thesine oculisenhancer

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 625-634 ◽  
Author(s):  
Claudio Punzo ◽  
Makiko Seimiya ◽  
Susanne Flister ◽  
Walter J. Gehring ◽  
Serge Plaza
Keyword(s):  
Binding Sites ◽  
Compound Eye ◽  
Eye Development ◽  
Targeted Mutagenesis ◽  
Hierarchical Network ◽  
Eyes Absent ◽  
Sine Oculis ◽  
Visual Systems ◽  
Rescue Experiment ◽  
Functional Involvement

Drosophila eye development is under the control of early eye specifying genes including eyeless (ey), twin of eyeless (toy), eyes absent (eya), dachshund (dac) and sine oculis (so). They are all conserved between vertebrates and insects and they interact in a combinatorial and hierarchical network to regulate each other expression. so has been shown to be directly regulated by ey through an eye-specific enhancer (so10). We further studied the regulation of this element and found that both Drosophila Pax6 proteins namely EY and TOY bind and positively regulate so10 expression through different binding sites. By targeted mutagenesis experiments, we disrupted these EY and TOY binding sites and studied their functional involvement in the so10 enhancer expression in the eye progenitor cells. We show a differential requirement for the EY and TOY binding sites in activating so10 during the different stages of eye development. Additionally, in a rescue experiment performed in the so1 mutant, we show that the EY and TOY binding sites are required for compound eye and ocellus development respectively. Altogether, these results suggest a differential requirement for EY and TOY to specify the development of the two types of adult visual systems, namely the compound eye and the ocellus.

The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1879-1886 ◽  
Author(s):  
M. Seimiya ◽  
W.J. Gehring
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Gene Family ◽  
Eye Development ◽  
Ectopic Expression ◽  
Amino Acid Sequence Similarity ◽  
Sine Oculis ◽  
High Amino Acid ◽  
Independent Mechanism ◽  
Ectopic Eyes

optix is a new member of the Six/so gene family from Drosophila that contains both a six domain and a homeodomain. Because of its high amino acid sequence similarity with the mouse Six3 gene, optix is considered to be the orthologous gene from Drosophila rather than sine oculis, as previously believed. optix expression was detected in the eye, wing and haltere imaginal discs. Ectopic expression of optix leads to the formation of ectopic eyes suggesting that optix has important functions in eye development. Although optix and sine oculis belong to the same gene family (Six/so) and share a high degree of amino acid sequence identity, there are a number of factors which suggest that their developmental roles are different: (1) the expression patterns of optix and sine oculis are clearly distinct; (2) sine oculis acts downstream of eyeless, whereas optix is expressed independently of eyeless; (3) sine oculis functions synergistically with eyes absent in eye development whereas optix does not; (4) ectopic expression of optix alone, but not of sine oculis can induce ectopic eyes in the antennal disc. These results suggest that optix is involved in eye morphogenesis by an eyeless-independent mechanism.

Genetic analysis of Pycr1 and Pycr2 in mice

Genetics ◽  
2021 ◽  
Author(s):  
Morgane G Stum ◽  
Abigail L D Tadenev ◽  
Kevin L Seburn ◽  
Kathy E Miers ◽  
Pak P Poon ◽  
...  
Keyword(s):  
Neuromuscular Disorders ◽  
Subcutaneous Fat ◽  
Mutant Mice ◽  
Loss Of Function ◽  
Proline Biosynthesis ◽  
Cell Counts ◽  
Chemically Induced ◽  
White Blood Cell Counts ◽  
Redundant Functions ◽  
Altered Lipid

Abstract The final step in proline biosynthesis is catalyzed by three pyrroline-5-carboxylate reductases, PYCR1, PYCR2, and PYCR3, which convert pyrroline-5-carboxylate (P5C) to proline. Mutations in human PYCR1 and ALDH18A1 (P5C Synthetase) cause Cutis Laxa (CL), whereas mutations in PYCR2 cause hypomyelinating leukodystrophy 10 (HLD10). Here, we investigated the genetics of Pycr1 and Pycr2 in mice. A null allele of Pycr1 did not show integument or CL-related phenotypes. We also studied a novel chemically-induced mutation in Pycr2. Mice with recessive loss-of-function mutations in Pycr2 showed phenotypes consistent with neurological and neuromuscular disorders, including weight loss, kyphosis, and hind-limb clasping. The peripheral nervous system was largely unaffected, with only mild axonal atrophy in peripheral nerves. A severe loss of subcutaneous fat in Pycr2 mutant mice is reminiscent of a CL-like phenotype, but primary features such as elastin abnormalities were not observed. Aged Pycr2 mutant mice had reduced white blood cell counts and altered lipid metabolism, suggesting a generalized metabolic disorder. PYCR1 and -2 have similar enzymatic and cellular activities, and consistent with previous studies, both were localized in the mitochondria in fibroblasts. Both PYCR1 and -2 were able to complement the loss of Pro3, the yeast enzyme that converts P5C to proline, confirming their activity as P5C reductases. In mice, Pycr1; Pycr2 double mutants were sub-viable and unhealthy compared to either single mutant, indicating the genes are largely functionally redundant. Proline levels were not reduced, and precursors were not increased in serum from Pycr2 mutant mice or in lysates from skin fibroblast cultures, but placing Pycr2 mutant mice on a proline-free diet worsened the phenotype. Thus, Pycr1 and -2 have redundant functions in proline biosynthesis, and their loss makes proline a semi-essential amino acid. These findings have implications for understanding the genetics of CL and HLD10, and for modeling these disorders in mice.

scholarly journals dE2F2-Independent Rescue of Proliferation in Cells Lacking an Activator dE2F1

2007 ◽  
Vol 27 (24) ◽  
pp. 8561-8570 ◽  
Author(s):  
Aaron M. Ambrus ◽  
Brandon N. Nicolay ◽  
Vanya I. Rasheva ◽  
Richard J. Suckling ◽  
Maxim V. Frolov
Keyword(s):  
Cell Cycle ◽  
Morphogenetic Furrow ◽  
Independent Manner ◽  
Dead Box ◽  
Cycle Arrest ◽  
Eye Disc ◽  
Severe Reduction ◽  
Functional Inactivation ◽  
Mutant Cells ◽  
Dependent Mechanism

ABSTRACT In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.

Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity determination in the Drosophila eye

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3619-3629 ◽  
Author(s):  
U. Weber ◽  
N. Paricio ◽  
M. Mlodzik
Keyword(s):  
Cell Fate ◽  
Genetic Interaction ◽  
Function Analysis ◽  
Loss Of Function ◽  
Planar Polarity ◽  
Jnk Signaling ◽  
Drosophila Eye ◽  
Polarity Determination ◽  
Signaling Components

Jun acts as a signal-regulated transcription factor in many cellular decisions, ranging from stress response to proliferation control and cell fate induction. Genetic interaction studies have suggested that Jun and JNK signaling are involved in Frizzled (Fz)-mediated planar polarity generation in the Drosophila eye. However, simple loss-of-function analysis of JNK signaling components did not show comparable planar polarity defects. To address the role of Jun and JNK in Fz signaling, we have used a combination of loss- and gain-of-function studies. Like Fz, Jun affects the bias between the R3/R4 photoreceptor pair that is critical for ommatidial polarity establishment. Detailed analysis of jun(−) clones reveals defects in R3 induction and planar polarity determination, whereas gain of Jun function induces the R3 fate and associated polarity phenotypes. We find also that affecting the levels of JNK signaling by either reduction or overexpression leads to planar polarity defects. Similarly, hypomorphic allelic combinations and overexpression of the negative JNK regulator Puckered causes planar polarity eye phenotypes, establishing that JNK acts in planar polarity signaling. The observation that Dl transcription in the early R3/R4 precursor cells is deregulated by Jun or Hep/JNKK activation, reminiscent of the effects seen with Fz overexpression, suggests that Jun is one of the transcription factors that mediates the effects of fz in planar polarity generation.

Induction of Drosophila eye development by decapentaplegic

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 271-278 ◽  
Author(s):  
F. Pignoni ◽  
S.L. Zipursky
Keyword(s):  
Pattern Formation ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Control ◽  
Transforming Growth Factor ◽  
Eye Development ◽  
Cluster Formation ◽  
Wing Disc ◽  
Posterior Edge ◽  
Gene Encoding ◽  
Eye Disc

The Drosophila decapentaplegic (dpp) gene, encoding a secreted protein of the transforming growth factor-beta (TGF-beta) superfamily, controls proliferation and patterning in diverse tissues, including the eye imaginal disc. Pattern formation in this tissue is initiated at the posterior edge and moves anteriorly as a wave; the front of this wave is called the morphogenetic furrow (MF). Dpp is required for proliferation and initiation of pattern formation at the posterior edge of the eye disc. It has also been suggested that Dpp is the principal mediator of Hedgehog function in driving progression of the MF across the disc. In this paper, ectopic Dpp expression is shown to be sufficient to induce a duplicated eye disc with normal shape, MF progression, neuronal cluster formation and direction of axon outgrowth. Induction of ectopic eye development occurs preferentially along the anterior margin of the eye disc. Ectopic Dpp clones situated away from the margins induce neither proliferation nor patterning. The Dpp signalling pathway is shown to be under tight transcriptional and post-transcriptional control within different spatial domains in the developing eye disc. In addition, Dpp positively controls its own expression and suppresses wingless transcription. In contrast to the wing disc, Dpp does not appear to be the principal mediator of Hedgehog function in the eye.

The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4819-4826 ◽  
Author(s):  
N.M. Bonini ◽  
Q.T. Bui ◽  
G.L. Gray-Board ◽  
J.M. Warrick
Keyword(s):  
Gene Function ◽  
Compound Eye ◽  
Eye Development ◽  
Control Gene ◽  
Eyes Absent ◽  
Regulatory Loop ◽  
The Relationship ◽  
Eye Formation ◽  
Master Control

The fly eyes absent (eya) gene which is essential for compound eye development in Drosophila, was shown to be functionally replaceable in eye development by a vertebrate Eya homolog. The relationship between eya and that of the eyeless gene, a Pax-6 homolog, critical for eye formation in both flies and man, was defined: eya was found to be essential for eye formation by eyeless. Moreover, eya could itself direct ectopic eye formation, indicating that eya has the capacity to function as a master control gene for eye formation. Finally, we show that eya and eyeless together were more effective in eye formation than either gene alone. These data indicate conservation of the pathway of eya function between flies and vertebrates; they suggest a model whereby eya/Eya gene function is essential for eye formation by eyeless/Pax-6, and that eya/Eya can in turn mediate, via a regulatory loop, the activity of eyeless/Pax-6 in eye formation.

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