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Isabelle Bachy

Publications and source records attributed to Isabelle Bachy.

10 recordsLinked to original sources
PubMed2006

Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity.

The roof plate (RP) of the midbrain shows an unusual plasticity, as it is duplicated or interrupted by experimental manipulations involving the mid/hindbrain organizer or FGF8. In previous experiments, we have found that FGF8 induces a local patterning center, the isthmic node, that is essential for the local development of a RP. Here, we show that the plasticity of the midbrain RP derives from two apparently antagonistic influences of FGF8. On the one hand, FGF8 widens beyond the neural folds the competence of the neuroepithelium to develop a RP by inducing the expression of LMX1B and WNT1. Ectopic overexpression of these two factors is sufficient to induce widely the expression of markers of the mature RP in the midbrain. On the other hand, FGF8 exerts a major destabilizing influence on RP maturation by controlling signaling by members of the TGFbeta superfamily belonging to the BMP, GDF and activin subgroups. We show in particular that FGF8 tightly modulates follistatin expression, thus progressively restraining the inhibitory influence of activin B on RP differentiation. These regulations, together with FGF8 triggered apoptosis, allow the formation of a RP progress zone at some distance from the FGF8 source. Posterior elongation of the RP is permitted when the source of FGF8 withdraws. Growth of the posterior midbrain neuroepithelium and convergent extension movements induced by FGF8 both contribute to increase the distance between the source of FGF8 and the maturing RP. Normally, the antagonistic regulatory interactions spread smoothly across the midbrain. Plasticity of midbrain RP differentiation probably results from an experimentally induced imbalance between regulatory pathways.

Animals↗
PubMed2006

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↗
PubMed2005

Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and AC8, during mouse brain development.

Type 1 and type 8 adenylate cyclases, AC1 and AC8, are membrane bound enzymes that produce cAMP in response to calcium entry and could thus control a large number of developmental processes. We provide a detailed spatiotemporal localization of these genes in the mouse brain during embryonic and postnatal life using in situ hybridization. AC1 gene expression begins early in embryonic life (before E13), and its expression is much more widespread than in adults. Transient expression of AC1 is found in the striatum, the dorsal thalamus, the trigeminal nerve nuclei, the Purkinje cells of the cerebellum, the interneurons of the hippocampus, and the retinal ganglion cells. In all these structures, the peak of AC1 gene expression occurs during early postnatal life, decreasing by P10. After P15, AC1 expression is confined to the hippocampus, the cerebral cortex, and to the granule cells of the cerebellum. AC8 gene expression also begins early in embryonic life (E12)--but in a more limited number of regions than in adults. AC8 expression is initially restricted to the epithalamus, the hypothalamus, the superior colliculus, the cerebellar anlage the proliferative zone of the rhombic lip, and the spinal cord. The expression increases and broadens during postnatal life, particularly in the thalamus and the cerebral cortex. A transient peak of AC8 expression is found in layer IV of the somatosensory cortex. Thus, AC1 and AC8 have an early developmental onset with complementary spatiotemporal distribution patterns: AC1 is most broadly distributed in embryonic life, whereas AC8 is most broadly expressed in adulthood. Transient expression of these genes designate areas that may be particularly sensitive to neural activity/calcium-modulated cAMP responses during development.

Adenylyl Cyclases↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMedDate not supplied

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.

Animals↗