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Sylvie Rétaux

Publications and source records attributed to Sylvie Rétaux.

12 recordsLinked to original sources

Dynamic expression of the LIM-homeodomain gene Lhx15 through larval brain development of the sea lamprey (Petromyzon marinus).

LIM-homeodomain genes encode a family of transcription factors with highly conserved roles in the patterning and regionalisation of the vertebrate brain. The expression of one of those genes, Lhx15, in the embryonic lamprey brain, characterises precise functional subdivisions. In order to analyse the non-embryonic development of the lamprey brain, we chose this gene to perform in situ hybridisations in Petromyzon marinus larvae of different ages. We demonstrate the usefulness of Lhx15 to follow the development and morphogenesis of brain structures and show the dynamical expression of this gene through time. Furthermore, we provide evidence for the evolutionary conservation of the expression of this gene in the spinal cord, notochord and urogenital system.

Animals↗

GABAergic specification in the basal forebrain is controlled by the LIM-hd factor Lhx7.

We present evidence for a temporal control of GABAergic neurotransmitter specification in the basal forebrain orchestrated by the LIM-homeodomain factor Lhx7. In Xenopus, using in vivo overexpression experiments, we show that x-Lhx7 and x-Nkx2.1 inhibit GABAergic specification in the Dlx-expressing areas of the forebrain (subpallium and diencephalon). In addition, x-Lhx7 almost totally represses GABAergic differentiation at early but not late embryonic stages in subpallial mouse primary neurons in culture, indicating that x-Lhx7 is not able to withdraw the GABAergic phenotype once it is acquired. Moreover, anatomical data show striking correlations between x-Lhx7 expression and the GABAergic/cholinergic phenotypes. These functional and anatomical observations suggest a sequential role for x-Lhx7 in neurotransmitter specification. Thus, x-Lhx7 would first prevent a pool of cells to become GABAergic early in development and then promote cholinergic differentiation later on in this pool. We propose two distinct modulatory roles for a single LIM-hd factor, depending on the developmental time window.

Animals↗

Organisation of the lamprey (Lampetra fluviatilis) embryonic brain: insights from LIM-homeodomain, Pax and hedgehog genes.

To investigate the embryonic development of the central nervous system of the lamprey Lampetra fluviatilis, we have isolated and analysed the expression patterns of members of the LIM-homeodomain, Pax, Hedgehog and Nkx2.1 families. Using degenerate RT-PCR, single representatives of Lhx1/Lhx5, Lhx2/Lhx9, Pax3/Pax7 and Hedgehog families could be isolated in L. fluviatilis. Expression analysis revealed that the lamprey forebrain presents a clear neuromeric pattern. We describe the existence of 4 embryonic diencephalic prosomeres whose boundaries can be identified by the combined and relative expressions of LfPax37, LfLhx15 and LfLhx29. This suggests that the embryonic lamprey and gnathostome forebrain are patterned in a highly similar manner. Moreover, analysis of the LfHh gene, which is expressed in the hypothalamus, zona limitans intrathalamica and floor plate, reveals the possible molecular origin of this neuromeric brain pattern. By contrast, LfHh and LfNkx2.1 expressions suggest major differences in patterning mechanisms of the ventral telencephalon when compared to gnathostomes. In summary, our findings highlight a neuromeric organisation of the embryonic agnathan forebrain and point to the possible origin of this organisation, which is thus a truly vertebrate character. They also suggest that Hh/Shh midline signalling might act as a driving force for forebrain evolution.

Amino Acid Sequence↗

LIM-homeodomain genes as territory markers in the brainstem of adult and developing Xenopus laevis.

We investigated expression patterns of the LIM-homeodomain (LIM-hd) genes x-Lhx1, x-Lhx2, x-Lhx5, and x-Lhx9 in the brainstem of Xenopus laevis during larval development and in the adult. The two groups of paralogous genes, x-Lhx1/x-Lhx5 and x-Lhx2/x-Lhx9, showed fundamentally different expression patterns, being expressed in ventral versus dorsal territories of the midbrain and hindbrain, respectively. Indeed, prominent expression of x-Lhx1/5 was found in the mesencephalic tegmentum and the hindbrain reticular formation, whereas conspicuous x-Lhx2/9 expression was observed in the torus semicircularis and isthmic nucleus. A few shared expression domains for the two pairs of paralogs included the optic tectum and the anterodorsal and pedunculopontine nuclei. In each structure, expression of the two paralogs was almost identical, indicating that the regulation of their expression in this part of the brain has evolved slightly since gene duplication occurred. Notable exceptions included the expression of x-Lhx1 but not x-Lhx5 in the Purkinje cells and the expression of x-Lhx9 but not x-Lhx2 in the lateral line nucleus. The analysis of LIM-hd expression patterns throughout development allowed the origin of given structures in early embryos to be traced back. x-Lhx1 and x-Lhx5 were relevant to locate the cerebellar anlage and to follow morphogenesis of the cerebellar plate and cerebellar nuclei. They also highlighted the rhombomeric organization of the hindbrain. On the other hand, x-Lhx2 and x-Lhx9 showed a dynamic spatiotemporal pattern relative to tectal development and layering, and x-Lhx9 was useful to trace back the origin of the isthmus in early development.

Animals↗

LIM-homeodomain genes as developmental and adult genetic markers of Xenopus forebrain functional subdivisions.

We have investigated the expression patterns of five LIM-homeodomain (LIM-hd) genes, x-Lhx1, x-Lhx2, x-Lhx5, x-Lhx7, and x-Lhx9 in the forebrain of the frog Xenopus laevis during larval development and in the adult. The results were analyzed in terms of neuromeric organization of the amphibian brain and of combinatorial LIM-hd code and showed that LIM-hd developmental transcription factors are particularly powerful to highlight the coherence of several groups or nuclei, to delineate subdivisions, and/or to clarify structures that are still a matter of debate. Among other findings, we bring substantial evidence for the following: (1) a dual origin of olfactory bulb neurons, based on x-Lhx5 expression; (2) the existence of a ventral pallium in frog, based on x-Lhx9 expression; (3) a multiple (pallial and subpallial) origin for the nuclei of the amygdaloid complex, based on distinct combinations of the five studied genes; (4) a clear homology between the Xenopus medial pallium and the mammalian hippocampus, based on x-Lhx2 pattern; and (5) a confirmed prosomeric organization of the diencephalon, based on alternating x-Lhx1/5 and x-Lhx2/9 expressions. In addition, the important expression levels for LIM-hd factors found throughout development and in the adult brain suggest a role for these genes in development and maintenance of neuronal specification and phenotype, as for example in the case of x-Lhx7 and cholinergic neurons. Moreover, following LIM-hd patterns throughout development points out to some of the migrations and morphogenetic movements, which give rise to the adult structures. Finally, the detailed description of the LIM-hd code in the developing and adult Xenopus forebrain provides interesting cues for the possible mechanisms of evolution of the vertebrate forebrain.

Animals↗

Cloning and developmental expression patterns of Dlx2, Lhx7 and Lhx9 in the medaka fish (Oryzias latipes).

We have isolated three homeodomain and LIM-homeodomain developmental transcription factors from the medaka fish (Oryzias latipes): OlDlx2, OlLhx7, and OlLhx9, and we have studied their expression patterns in the developing and adult brain. This analysis showed that OlDlx2 and OlLhx7 (together with OlNkx2.1b) delineate the subpallial divisions of the medaka telencephalon, and that OlLhx9 exhibits a typical and specific topology of expression in the pallium and diencephalic neuromeres. The expression patterns of these three genes, when compared in details with those of their tetrapod homologs, reveal both commonalities and differences in the basic organization of the developing teleost and vertebrate forebrain.

Amino Acid Sequence↗

Lhx9 and lhx9alpha: differential biochemical properties and effects on neuronal differentiation.

The Lhx9 LIM-homeodomain transcription factor and its truncated isoform Lhx9alpha are generated by alternative splicing of the Lhx9 gene. Here we investigated the differential functional properties of these two isoforms. Lhx9alpha, which lacks parts of the homeodomain, was unable to bind DNA in EMSA experiments, but was able to associate with CLIM cofactors in GST pull-down assays. In transfection experiments in PC12 cells, Lhx9alpha fusion constructs systematically showed a nuclear localization, as opposed to Lhx9 fusion constructs, which also localized to the cytoplasm. Moreover, Lhx9 increased NGF-induced neuronal differentiation of PC12 cells. Lhx9alpha, on the other hand, did not significantly increase neuronal differentiation but had an effect on the morphology of PC12 cells. Finally, as tested by RT-PCR experiments on transfected PC12 cells, Lhx9 was not able to induce the transcription of Lhx9alpha. Our results show significantly different functional properties for Lhx9 and Lhx9alpha, and suggest that Lhx9alpha can compete away limiting amounts of nuclear CLIM cofactors. Thus, Lhx9 and Lhx9alpha isoforms could be implicated in regulating various aspects of neuronal differentiation.

Animals↗

Pallial origin of mitral cells in the olfactory bulbs of Xenopus.

We used two developmental transcription factors, x-Eomes (T-box family) and x-Lhx5 (LIM-homeodomain family), to follow the origin and development of the olfactory bulbs in Xenopus. During embryonic and larval development, x-Eomes and x-Lhx5 were expressed in highly similar patterns, in the lateral and latero-ventral wall of the pallium. In adults, both markers were strongly and specifically expressed in mitral cells, i.e., in the projection neurons of the main and accessory olfactory bulbs. These results demonstrate the pallial origin of the olfactory projecting cells in Xenopus. Combined with previous results suggesting a subpallial origin for olfactory interneurons, these findings emphasize the dual origin of different neuronal populations in the bulbs of anamniotes, and suggest that this organization is a shared feature of tetrapods.

Animals↗

Defining pallial and subpallial divisions in the developing Xenopus forebrain.

To shed light on the organisation of the Xenopus laevis telencephalon, we have used two sets of developmental regulators: genes acting in early regional specification (x-Dll3, x-Nkx2.1, x-Emx1, x-Pax6, x-Eomes) or in cell determination (x-Lhx5 and x-Lhx7). After expression patterns analysis, separately or combined, on whole-mount brains and serial sections, we identify the Xenopus pallium and subpallium, and the subdivisions herein. The data show a conservation of the same basic Bauplan for Xenopus forebrain patterning compared to other vertebrates, and suggest the possibility for LIM-homeodomain genes to be candidate downstream target of the regionalization genes. Comparing the relative sizes of the deduced subdivisions, Xenopus seems to have an intermediate phylogenetic position in terms of pallium contribution to the telencephalon, and ventral pallium contribution to the pallium.

Animals↗

Expression of the LIM-homeodomain gene Lmx1a (dreher) during development of the mouse nervous system.

The expression pattern of Lmx1a, a LIM-homeodomain gene disrupted in the dreher mouse neurological mutant, is described during development. Lmx1a is predominantly expressed in the developing nervous system from embryonic day E8.5 to adulthood, in restricted areas. Major expression domains include the dorsal midline (roof plate) of the neural tube, the cortical hem, the otic vesicles, the developing cerebellum and the notochord. The Lmx1a expression pattern is therefore well correlated with the various aspects of the phenotype of the dreher mutant mice.

Animals↗

A short history of LIM domains (1993-2002): from protein interaction to degradation.

The LIM domain is a cysteine-rich zinc-finger motif found in a large family of proteins. In LIM-homeodomain (LIM-hd) transcription factors and LIM-only (LMO) factors, the LIM domains are responsible for key interactions with co-activators, co-repressors, competitors, and other transcription factors, and are therefore of considerable importance for the regulation of associated transcriptional activity. In this review, the authors describe the progressive discoveries of NLI/Ldb/CLIM, LMO and RLIM, and discuss how the field was very recently updated by the finding that LIM-hd transcriptional activity is controlled by regulated degradation of cofactors and LIM-hd themselves.

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