Hoxd gene regulation in the developing caecum

[...] In this project, we investigated the qualitative and quantitative profile of expression of the HoxD complex in the developing caecum of wild-type animals. [... click on "Download fulltext" for full abstract

Multiple Enhancers Regulate Hoxd Genes and the Hotdog LncRNA during Cecum Budding

Hox genes are required for the development of the intestinal cecum, a major organ of plant-eating species. We have analyzed the transcriptional regulation of Hoxd genes in cecal buds and show that they are controlled by a series of enhancers located in a gene desert flanking the HoxD cluster. The start site of two opposite long noncoding RNAs (lncRNAs), Hotdog and Twin of Hotdog, selectively contacts the expressed Hoxd genes in the framework of a topological domain, coinciding with robust transcription of these genes during cecum budding. Both lncRNAs are specifically transcribed in the cecum, albeit bearing no detectable function in trans. Hedgehogs have kept this regulatory potential despite the absence of the cecum, suggesting that these mechanisms are used in other developmental situations. In this context, we discuss the implementation of a common "budding toolkit" between the cecum and the limbs

A function for all posterior Hoxd genes during digit development?

Background: Four posterior Hoxd genes, from Hoxd13 to Hoxd10, are collectively regulated during the development of tetrapod digits. Besides the well-documented role of Hoxd13, the function of the neighboring genes has been difficult to evaluate due to the close genetic linkage and potential regulatory interferences. We used a combination of five small nested deletions in cis, involving from two to four consecutive genes of the Hoxd13 to Hoxd9 loci, in mice, to evaluate their combined functional importance. Results: We show that deletions leading to a gain of function of Hoxd13, via regulatory re-allocation, generate abnormal phenotypes, in agreement with the dominant negative role of this gene. We also show that Hoxd10, Hoxd11, and Hoxd12 all seem to play a genuine role in digit development, though less compelling than that of Hoxd13. In contrast, the nearby Hoxd9 contributed no measurable function in digits. Conclusions: We conclude that a slight and transient deregulation of Hoxd13 expression can readily affect the relative lengths of limb segments and that all posterior Hoxd genes likely contribute to the final limb morphology. We discuss the difficulty to clearly assess the functional share of individual genes within such a gene family, where closely located neighbors, coding for homologous proteins, are regulated by a unique circuitry and all contribute to shape the distal parts of our appendages. Developmental Dynamics 241:792-802, 2012. © 2012 Wiley Periodicals, Inc

Multiframe SURE-LET denoising of timelapse fluorescence microscopy images

Due to the random nature of photon emission and the various internal noise sources of the detectors, real timelapse fluorescence microscopy images are usually modeled as the sum of a Poisson process plus some Gaussian white noise. In this paper, we propose an adaptation of our SURE-LET denoising strategy to take advantage of the potentially strong similarities between adjacent frames of the observed image sequence. To stabilize the noise variance, we first apply the generalized Anscombe transform using suitable parameters automatically estimated from the observed data. With the proposed algorithm, we show that, in a reasonable computation time, real fluorescence timelapse microscopy images can be denoised with higher quality than conventional algorithms

The constrained architecture of mammalian Hox gene clusters

In many animal species with a bilateral symmetry,; Hox; genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate; Hox; clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the; HoxD; cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian; Hox; clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of; Hox; clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in; cis;