Biomedical subjects

Juan J Tena

Publications and source records attributed to Juan J Tena.

4 recordsLinked to original sources

PubMed2006

Odd-skipped genes encode repressors that control kidney development.

Odd-skipped family of proteins (Odd in Drosophila and Osr in vertebrates) are evolutionarily conserved zinc finger transcription factors. Two Osr genes are present in mammalian genomes, and it was recently reported that Osr1, but not Osr2, is required for murine kidney development. Here, we show that in Xenopus and zebrafish both Osr1 and Osr2 are necessary and sufficient for the development of the pronephros. Osr genes are expressed in early prospective pronephric territories, and morphants for either of the two genes show severely impaired kidney development. Conversely, overexpression of Osr genes promotes formation of ectopic kidney tissue. Molecularly, Osr proteins function as transcriptional repressors during kidney formation. We also show that Drosophila Odd induces kidney tissue in Xenopus. This might be accomplished through recruitment of Groucho-like co-repressors. Odd genes may also be required for proper development of the Malpighian tubules, the Drosophila renal organs. Our results highlight the evolutionary conserved involvement of Odd-skipped transcription factors in the development of kidneys.

Animals↗

PubMed2006

Cracking the genome's second code: enhancer detection by combined phylogenetic footprinting and transgenic fish and frog embryos.

Genes involved in vertebrate development are unusually enriched for highly conserved non-coding sequence elements. These regions are readily detected in silico, by genome-wide sequence comparisons between different vertebrates, from mammals to fish (phylogenetic footprinting). It follows that sequence conservation must be the result of positive selection for an essential physiological role. An obvious possibility is that these conserved sequences possess regulatory or structural functions important for gene expression and, thus, an in vivo assay becomes necessary. We have developed a rapid testing system using zebrafish and Xenopus laevis embryos that allows us to assign transcriptional regulatory functions to conserved non-coding sequence elements. The sequences are cloned into a vector containing a minimal promoter and the GFP reporter, and are assayed for their putative cis-regulatory activity in zebrafish or Xenopus transgenic experiments. Vectors used include plasmid DNA and the Tol2 transposon system in fish and X. laevis. We have followed this logic to detect and analyze conserved elements in an intergenic region present in the Iroquois (Irx) gene clusters of zebrafish, Xenopus tropicalis, Fugu rubripes and mouse. We have assayed approximately 50 of these conserved elements and shown that the majority behave as modular positive regulatory elements (enhancers) that contribute to specific temporal and spatial domains that are part of the endogenous gene expression pattern. Moreover, comparison of the activity of cognate Irx enhancers from different organisms demonstrates that conservation of sequence is accompanied by in vivo functional conservation across species. Finally, for some of the most conserved elements, we have been able to identify a critical core sequence, essential for correct enhancer function.

Animals↗

PubMed2005

A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts.

Recent studies of the genome architecture of vertebrates have uncovered two unforeseen aspects of its organization. First, large regions of the genome, called gene deserts, are devoid of protein-coding sequences and have no obvious biological role. Second, comparative genomics has highlighted the existence of an array of highly conserved non-coding regions (HCNRs) in all vertebrates. Most surprisingly, these structural features are strongly associated with genes that have essential functions during development. Among these, the vertebrate Iroquois (Irx) genes stand out on both fronts. Mammalian Irx genes are organized in two clusters (IrxA and IrxB) that span >1 Mb each with no other genes interspersed. Additionally, a large number of HCNRs exist within Irx clusters. We have systematically examined the enhancer activity of HCNRs from the IrxB cluster using transgenic Xenopus and zebrafish embryos. Most of these HCNRs are active in subdomains of endogenous Irx expression, and some are candidates to contain shared enhancers of neighboring genes, which could explain the evolutionary conservation of Irx clusters. Furthermore, HCNRs present in tetrapod IrxB but not in fish may be responsible for novel Irx expression domains that appeared after their divergence. Finally, we have performed a more detailed analysis on two IrxB ultraconserved non-coding regions (UCRs) duplicated in IrxA clusters in similar relative positions. These four regions share a core region highly conserved among all of them and drive expression in similar domains. However, inter-species conserved sequences surrounding the core, specific for each of these UCRs, are able to modulate their expression.

Animals↗

PubMed2004

Cerebellar grafting in the oculomotor system as a model to study target influence on adult neurons.

In the last decades, there have been many efforts directed to gain a better understanding on adult neuron-target cell relationships. Embryonic grafts have been used for the study of neural circuit rewiring. Thus, using several donor neuronal tissues, such as cerebellum or striatum, developing grafted cells have been shown to have the capability of substituting neural cell populations and establishing reciprocal connections with the host. In addition, different lesion paradigms have also led to a better understanding of target dependence in neuronal cells. Thus, for example, axotomy induces profound morphofunctional changes in adult neurons, including the loss of synaptic inputs and discharge alterations. These alterations are probably due to trophic factor loss in response to target disconnection. In this review, we summarize the different strategies performed to disconnect neurons from their targets, and the effects of target substitution, performed by tissue grafting, upon neural properties. Using the oculomotor system-and more precisely the abducens internuclear neurons-as a model, we describe herein the effects of disconnecting a population of central neurons from its natural target (i.e., the medial rectus motoneurons at the mesencephalic oculomotor nucleus). We also analyze target-derived influences in the structure and physiology of these neurons by using cerebellar embryonic grafts as a new target for the axotomized abducens internuclear neurons.

Abducens Nerve↗