Genetic control of development of the mushroom bodies, the associative learning centers in the
 Drosophila
 brain, by the
 eyeless, twin of eyeless
 , and
 dachshund
 genes

Kurusu, Mitsuhiko; Nagao, T.; Walldorf, Uwe; Flister, Susanne; Gehring, Walter; Furukubo-Tokunaga, Katsuo

doi:10.1073/pnas.040564497

Cited by 123 publications

(129 citation statements)

References 33 publications

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“…In both vertebrates and invertebrates dachshund displays a complex temporal and spatial pattern of expression, and the gene product is critical in the development of the central nervous system, sensory organs, and limbs [19][20][21][22]23].…”

Section: Introductionmentioning

confidence: 99%

In vivo characterization of a vertebrate ultraconserved enhancer

et al. 2005

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Genomic sequence comparisons between human, mouse and pufferfish (Takifugu rubripes (Fugu)) have revealed a set of extremely conserved noncoding sequences. While this high degree of sequence conservation suggests severe evolutionary constraint and predicts a lack of tolerance to change in order to retain in vivo functionality, such elements have been minimally explored experimentally. In this study, we describe the in-depth characterization of an ancient conserved enhancer, Dc2 located near the dachshund gene, which displays a human-Fugu identity of 84% over 424 basepairs (bp). In addition to this large overall conservation, we find that Dc2 is characterized by the presence of a large block of sequence (144 bp) that is completely identical between human, mouse, chicken, zebrafish and Fugu. Through the testing of reporter vector constructs in transgenic mice, we observed that the 424 bp Dc2 conserved element is necessary and sufficient for brain tissue enhancer activity. In vivo analyses also revealed that the 144 bp 100% conserved sequence is necessary, but not sufficient, to replicate Dc2 enhancer function. However, the introduction of two separate 16 bp insertions into the highly conserved enhancer core did not cause any detectable modification of its in vivo activity. Our observations indicate that the 144 bp 100% conserved element is tolerant of change at least at the resolution of this transgenic mouse assay and suggest that purifying selection on Dc2 sequence might not be as strong as we predicted or that some unknown property also constrains this highly conserved enhancer sequence. Thank you for your letter of February 15 th and for the reviewers' comments on our manuscript entitled "In Vivo Characterization of a Vertebrate Ultra-conserved Enhancer", by Poulin et al. We have addressed the reviewers' concerns in a revised manuscript, which we are resubmitting for your consideration.Our detailed response is as follows:Reviewer #21. Abstract -last sentence should read: "tolerant of change at least AT the resolution…"We have changed this typo. 2.Introduction paragraph four (page 4), first sentence. Statement "which is involved in embryonic development" is too vague. Please state, briefly, the function of DACH.We have added an introduction description of DACHs known function and reference to its Drosophila homolog. 3.Introduction paragraph four (page 4). When first introducing Dc2, please define it as a conserved, functional element at DACH (i.e., since the Dc nomenclature was not used previously in the text).We have made this change. 4.Introduction paragraph four (page 4). Please provide a reference for the statement "known degeneracy of the sequences recognized by transcription factors".We have added a reference. 5.Results paragraph one (page 5), first sentence. Please restate the locus (DACH) at which Dc2 resides.We have made this change. 6.Results "Refinement of the Minimal Necessary Dc2 Enhancer". Authors state that the 424 bp fragment drives expression pattern in transgenics that is "indistingu...

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Section: Introductionmentioning

confidence: 99%

In vivo characterization of a vertebrate ultraconserved enhancer

et al. 2005

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“…Drosophila dachshund mutant flies lack eyes, have truncated limbs, and exhibit brain abnormalities (22,25,26). Given the structural and expression similarities between Drosophila dachshund and mouse Dach1, we hypothesized that Dach1 mutant mice would exhibit defects in eye, limb, and/or brain development.…”

Section: Fig 2 Targeted Disruption Ofmentioning

confidence: 99%

“…Expression analysis of Dach1 demonstrates that it is expressed in the developing retina, limbs, and nervous system, which is analogous to the expression pattern of Drosophila dachshund (4,11,15,25). As dachshund mutant flies lack eyes, have truncated limbs, and display defects in brain development, the structural and expression similarities shared between Dach1 and dachs-hund suggest a similar role for Dach1 during vertebrate development (22,25,26).…”

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confidence: 99%

Dach1 Mutant Mice Bear No Gross Abnormalities in Eye, Limb, and Brain Development and Exhibit Postnatal Lethality

Davis¹,

Shen

Sandler³

et al. 2001

Molecular and Cellular Biology

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Drosophila dachshund is necessary and sufficient for compound eye development and is required for normal leg and brain development. A mouse homologue of dachshund, Dach1, is expressed in the developing retina and limbs, suggesting functional conservation of this gene. We have generated a loss-of-function mutation in Dach1 that results in the abrogation of the wild-type RNA and protein expression pattern in embryos. Homozygous mutants survive to birth but exhibit postnatal lethality associated with a failure to suckle, cyanosis, and respiratory distress. The heart, lungs, kidneys, liver, and skeleton were examined to identify factors involved in postnatal lethality, but these organs appeared to be normal. In addition, blood chemistry tests failed to reveal differences that might explain the lethal phenotype. Gross examination and histological analyses of newborn eyes, limbs, and brains revealed no detectable abnormalities. Since Dach1 mutants die shortly after birth, it remains possible that Dach1 is required for postnatal development of these structures. Alternatively, an additional Dach homologue may functionally compensate for Dach1 loss of function.

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“…The Drosophila Pax6 homolog eyeless has essential roles in the development of the eye and brain in Drosophila (Quiring et al, 1994;Halder et al, 1995;Noveen et al, 2000;Kurusu et al, 2000;Callaerts et al, 2001). During eye development, eyeless is initially expressed in the embryonic eye anlagen and subsequently throughout the eye part of the eye-antennal imaginal disc in first and second instar larvae.…”

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confidence: 99%