Identification of an upstream regulatory element reveals a novel requirement for Ind activity in maintaining ind expression

Ohlen, Tonia L. Von; Harvey, Canda; Panda, Manasa Kumar

doi:10.1016/j.mod.2006.11.003

Cited by 12 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like snail, the intermediate neuroblasts defective (ind) gene also has a distally located enhancer and another that is located in the proximal position. Similar to what we see at the snail locus, the distal CRM has documented repression associated with it, whereas the proximally located element functions through positive autoregulatory feedback (Stathopoulos and Levine, 2005;Von Ohlen et al, 2007). We suggest that keeping repressors located at a distance from the promoter supports flexibility in reiterative reactivation of genes throughout the course of development.…”

Section: Crms Are Organized Along the Dna To Support Effective Transcsupporting

confidence: 75%

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

2011

View full text Add to dashboard Cite

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression.

show abstract

Section: Crms Are Organized Along the Dna To Support Effective Transcsupporting

confidence: 75%

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

2011

View full text Add to dashboard Cite

show abstract

“…That is, there was ectopic expression of the lacZ message in a domain that corresponded to the EveSt2 domain (Figure 3I). The identification of an activation domain is not entirely surprising because Ind is necessary to maintain its own expression (Von Ohlen et al, 2007b). Finally, the fragment of Ind including the homeodomain and C-terminus had no obvious effect on reporter gene expression.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the ability of Vnd and Ind to regulate gene expression appears to be intimately associated with their ability to interact with other co-regulators. Furthermore, both Vnd and Ind are required to maintain their own expression (Saunders et al, 1998; Von Ohlen et al, 2007b). The auto-regulatory role for both Vnd and Ind appears to be a maintenance role and not an initiation function.…”

Section: Introductionmentioning

confidence: 99%

Identification of Ind transcription activation and repression domains required for dorsoventral patterning of the CNS

Ohlen

Moses

2009

Mechanisms of Development

Self Cite

View full text Add to dashboard Cite

Specification of cell fates across the dorsoventral axis of the central nervous system in Drosophila involves the subdivision of the neuroectoderm into three domains that give rise to three columns of neural precursor cells called neuroblasts. Ventral nervous system defective (Vnd), Intermediate neuroblasts defective (Ind) and Muscle segment homeobox (Msh) are expressed in the three columns from ventral to dorsal, respectively. The products of these genes play multiple important roles in formation and specification of the embryonic nervous system. Ind for example is known to play roles in two important processes. First, Ind is essential for formation of neuroblasts conjunction with SoxB class transcription factors. Sox class transcription factors are known to specify neural stem cells in vertebrates. Second, Ind plays an important role in patterning the CNS in conjunction with, vnd and msh, which is also similar to how vertebrates pattern their neural tube. This work focuses two important aspects of Ind function. First, we used multiple approaches to identify and characterize specific domains within the protein that confer repressor or activator ability. Currently, little is known about the presence of activation or repression domains within Ind. Here we show that transcriptional repression by Ind requires multiple conserved domains within the protein, and that Ind has a transcriptional activation domain. Specifically, we have identified a novel domain, the Pst domain, that has transcriptional repression ability and appears to act independent of interaction with the co-repressor Groucho. This domain is highly conserved among insect species, but is not found in vertebrate Gsh class homeodomain proteins. Second, we show that Ind can and does repress vnd expression, but does so in a stage specific manner. We conclude from this that the function of Ind in regulating vnd expression is one of refinement and maintenance of the dorsal border.

show abstract

“…We suggest those that are retained must rely on a Dorsal-independent mechanism to support expression along the DV axis. For example, several genes (e.g., sim and vnd ) switch to autoregulatory feedback mechanisms to retain expression within the same domain and thereby no longer depend on Dorsal to support activation (Nambu et al, 1991; Von Ohlen et al, 2007). …”

Section: Discussionmentioning

confidence: 99%

Dorsal-Ventral Gene Expression in the Drosophila Embryo Reflects the Dynamics and Precision of the Dorsal Nuclear Gradient

et al. 2012

View full text Add to dashboard Cite

SUMMARY Patterning of the dorsal-ventral axis in the early Drosophila embryo depends on the nuclear distribution of the Dorsal transcription factor. Using live two-photon light-sheet microscopy, we quantified the nuclear Dorsal gradient in space and time and found that its amplitude and basal levels display oscillations throughout early embryonic development. These dynamics raise questions regarding how cells can reproducibly establish patterns of gene expression from a rapidly varying signal. We therefore quantified domains of Dorsal target genes, discovering their expression patterns are also dynamic. Computational modeling of this system reveals a correlation between Dorsal gradient dynamics and changes in target gene expression and suggests that these dynamics, together with time averaging of noise, results in the formation of graded gene expression borders in regions where the gradient is nearly flat. We propose that mRNA levels remain plastic during transient signaling events, allowing tissues to refine patterns in the face of genetic or environmental variation.

show abstract

Identification of an upstream regulatory element reveals a novel requirement for Ind activity in maintaining ind expression

Cited by 12 publications

References 25 publications

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

Identification of Ind transcription activation and repression domains required for dorsoventral patterning of the CNS

Dorsal-Ventral Gene Expression in the Drosophila Embryo Reflects the Dynamics and Precision of the Dorsal Nuclear Gradient

Contact Info

Product

Resources

About