scholarly journals The time to measure positional information: maternal Hunchback is required for the synchrony of the Bicoid transcriptional response at the onset of zygotic transcription

Development ◽  
2010 ◽  
Vol 137 (16) ◽  
pp. 2795-2804 ◽  
Author(s):  
A. Porcher ◽  
A. Abu-Arish ◽  
S. Huart ◽  
B. Roelens ◽  
C. Fradin ◽  
...  
2018 ◽  
Author(s):  
Tanguy Lucas ◽  
Huy Tran ◽  
Carmina Angelica Perez Romero ◽  
Aurélien Guillou ◽  
Cécile Fradin ◽  
...  

AbstractMorphogen gradients provide concentration-dependent positional information along polarity axes. Although the dynamics of establishment of these gradients is well described, precision and noise in the downstream activation processes remain elusive. A simple paradigm to address these questions is the Bicoid morphogen gradient that elicits a rapid step-like transcriptional response in young fruit fly embryos. Focusing on the expression of the main Bicoid target, hunchback (hb), at the onset of zygotic transcription, we used the MS2-MCP approach which combines fluorescent labeling of nascent mRNA with live imaging at high spatial and temporal resolution. Removing 36 putative Zelda binding sites unexpectedly present in the original MS2 reporter, we show that the 750 bp of the hb promoter are sufficient to recapitulate endogenous expression at the onset of zygotic transcription. After each mitosis, in the anterior, expression is turned on to rapidly reach a plateau with all nuclei expressing the reporter. Consistent with a Bicoid dose-dependent activation process, the time period required to reach the plateau increases with the distance to the anterior pole. Remarkably, despite the challenge imposed by frequent mitoses and high nuclei-to-nuclei variability in transcription kinetics, it only takes 3 minutes at each interphase for the MS2 reporter loci to measure subtle differences in Bicoid concentration and establish a steadily positioned and steep (Hill coefficient ~ 7) expression boundary. Modeling based on cooperativity between the 6 known Bicoid binding sites in the hb promoter region and assuming rate limiting concentrations of the Bicoid transcription factor at the boundary is able to capture the observed dynamics of pattern establishment but not the steepness of the boundary. This suggests that additional mechanisms are involved in the steepness of the response.


2017 ◽  
Vol 4 (4) ◽  
pp. 160913 ◽  
Author(s):  
Nicoletta Carucci ◽  
Emanuele Cacci ◽  
Paola S. Nisi ◽  
Valerio Licursi ◽  
Yu-Lee Paul ◽  
...  

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.


Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 81-93 ◽  
Author(s):  
M.C. Mullins ◽  
M. Hammerschmidt ◽  
D.A. Kane ◽  
J. Odenthal ◽  
M. Brand ◽  
...  

We identified 6 genes that are essential for specifying ventral regions of the early zebrafish embryo. Mutations in these genes cause an expansion of structures normally derived from dorsal-lateral regions of the blastula at the expense of ventrally derived structures. A series of phenotypes of varied strengths is observed with different alleles of these mutants. The weakest phenotype is a reduction in the ventral tail fin, observed as a dominant phenotype of swirl, piggytail, and somitabun and a recessive phenotype of mini fin, lost-a-fin and some piggytail alleles. With increasing phenotypic strength, the blood and pronephric anlagen are also reduced or absent, while the paraxial mesoderm and anterior neuroectoderm is progressively expanded. In the strong phenotypes, displayed hy homozygous embryos of snailhouse, swirl and somitabun, the somites circle around the embryo and the midbrain region is expanded laterally. Several mutations in this group of genes are semidominant as well as recessive indicating a strong dosage sensitivity of the processes involved. Mutations in the piggytail gene display an unusual dominance that depends on both a maternal and zygotic heterozygous genotype, while somitabun is a fully penetrant dominant maternal-effect mutation. The similar and overlapping phenotypes of mutants of the 6 genes identified suggest that they function in a common pathway, which begins in oogenesis, but also depends on factors provided after the onset of zygotic transcription, presumably during blastula stages. This pathway provides ventral positional information, counteracting the dorsalizing instructions of the organizer, which is localized in the dorsal shield.


2020 ◽  
Author(s):  
Robert Calin-Jageman ◽  
Irina Calin-Jageman ◽  
Tania Rosiles ◽  
Melissa Nguyen ◽  
Annette Garcia ◽  
...  

[[This is a Stage 2 Registered Report manuscript now accepted for publication at eNeuro. The accepted Stage 1 manuscript is posted here: https://psyarxiv.com/s7dft, and the pre-registration for the project is available here (https://osf.io/fqh8j, 9/11/2019). A link to the final Stage 2 manuscript will be posted after peer review and publication.]] There is fundamental debate about the nature of forgetting: some have argued that it represents the decay of the memory trace, others that the memory trace persists but becomes inaccessible due to retrieval failure. These different accounts of forgetting lead to different predictions about savings memory, the rapid re-learning of seemingly forgotten information. If forgetting is due to decay, then savings requires re-encoding and should thus involve the same mechanisms as initial learning. If forgetting is due to retrieval failure, then savings should be mechanistically distinct from encoding. In this registered report we conducted a pre-registered and rigorous test between these accounts of forgetting. Specifically, we used microarray to characterize the transcriptional correlates of a new memory (1 day after training), a forgotten memory (8 days after training), and a savings memory (8 days after training but with a reminder on day 7 to evoke a long-term savings memory) for sensitization in Aplysia californica (n = 8 samples/group). We found that the re-activation of sensitization during savings does not involve a substantial transcriptional response. Thus, savings is transcriptionally distinct relative to a newer (1-day old) memory, with no co-regulated transcripts, negligible similarity in regulation-ranked ordering of transcripts, and a negligible correlation in training-induced changes in gene expression (r = .04 95% CI [-.12, .20]). Overall, our results suggest that forgetting of sensitization memory represents retrieval failure.


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