Studying non-mammalian models? Not a fool's ERRand!

Through studies in mammalian model systems, the estrogen-receptor-related receptor (ERR) alpha, an orphan nuclear receptor, has been shown to interfere with estrogen signaling and might therefore be an interesting pharmaceutical target in estrogen-related diseases. ERRalpha is also involved in energy storage and consumption, and its modulation might be of relevance in the treatment of obesity and diabetes. Recent data have also been published on the effects of this receptor, as well as other members of the ERR family, in non-mammalian animal model systems. Besides indications concerning their mechanisms of action, this analysis demonstrated a role for ERRalpha in controlling cellular movements, and suggested that ERRs might be implicated in a more subtle range of processes than originally envisioned

Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature

Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis. However, the mechanisms underlying detection of CSF flow in the central canal of the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the cfap298tm304 mutant, reduction of cilia motility slows transport posteriorly down the central canal and abolishes spontaneous activity of CSF-contacting neurons (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium activity and single channel opening. Recording from isolated CSFcNs in vitro, we show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure. Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of natural curvature of the spine

Unexpected Novel Relational Links Uncovered by Extensive Developmental Profiling of Nuclear Receptor Expression

Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes) using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily

La voie Hippo contrôle la croissance des organes au cours du développement

Les mécanismes moléculaires contrôlant la taille des organes au cours du développement sont encore mal compris. La voie Hippo, récemment découverte chez la mouche drosophile, contrôle l’arrêt de la croissance des organes quand ils ont atteint leur nombre final de cellules. Pour ce faire, cette cascade de phosphorylation réprime la transcription de gènes favorisant la prolifération et la survie. La mutation des gènes responsables de cette répression a donc pour effet de produire des excroissances. Les régulations agissant en amont de cette voie commencent à être identifiées et sont nombreuses. Cette voie et ses fonctions de contrôle de la croissance sont conservées chez les mammifères, et la confrontation du modèle de la drosophile et des modèles mammifères est riche d’enseignements pour la compréhension de processus humains, dont celui qui conduit au développement de cancers

The ERRalpha orphan nuclear receptor controls morphogenetic movements during zebrafish gastrulation

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Specification and Positioning of Parasegment Grooves in Drosophila

AbstractDevelopmental boundaries ensure that cells fated to participate in a particular structure are brought together or maintained at the appropriate locale within developing embryos. Parasegment grooves mark the position of boundaries that separate every segment of the Drosophila embryo into anterior and posterior compartments. Here, we dissect the genetic hierarchy that controls the formation of this morphological landmark. We report that primary segment polarity genes (engrailed, hedgehog and wingless) are not involved in specifying the position of parasegment grooves. Wingless signalling plays only a permissive role by triggering the formation of grooves at cellular interfaces defined by the ON/OFF state of expression of the earlier acting pair-rule genes eve and ftz. We suggest that the transcription factors encoded by these genes activate two programmes in parallel: a cell fate programme mediated by segment polarity genes and a boundary/epithelial integrity programme mediated by unknown target genes

Lorsque l'enfant grandit : entre dépendance et autonomie

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Lorsque l'enfant grandit : entre dépendance et autonomie

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Adrenergic activation modulates the signal from the Reissner fiber to cerebrospinal fluid-contacting neurons during development

International audienceThe cerebrospinal fluid (CSF) contains an extracellular thread conserved in vertebrates, the Reissner fiber, which controls body axis morphogenesis in the zebrafish embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required in vivo for the expression of urp2, a neuropeptide expressed in CSF-cNs. We show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results show that the Reissner fiber acts on CSF-cNs and thereby contributes to establish body axis morphogenesis, and suggest it does so by controlling the availability of a chemical signal in the CSF

Regulation of the apical extension morphogenesis tunes the mechanosensory response of microvilliated neurons.

Multiple types of microvilliated sensory cells exhibit an apical extension thought to be instrumental in the detection of sensory cues. The investigation of the mechanisms underlying morphogenesis of sensory apparatus is critical to understand the biology of sensation. Most of what we currently know comes from the study of the hair bundle of the inner ear sensory cells, but morphogenesis and function of other sensory microvilliated apical extensions remain poorly understood. We focused on spinal sensory neurons that contact the cerebrospinal fluid (CSF) through the projection of a microvilliated apical process in the central canal, referred to as cerebrospinal fluid-contacting neurons (CSF-cNs). CSF-cNs respond to pH and osmolarity changes as well as mechanical stimuli associated with changes of flow and tail bending. In vivo time-lapse imaging in zebrafish embryos revealed that CSF-cNs are atypical neurons that do not lose their apical attachment and form a ring of actin at the apical junctional complexes (AJCs) that they retain during differentiation. We show that the actin-based protrusions constituting the microvilliated apical extension arise and elongate from this ring of actin, and we identify candidate molecular factors underlying every step of CSF-cN morphogenesis. We demonstrate that Crumbs 1 (Crb1), Myosin 3b (Myo3b), and Espin orchestrate the morphogenesis of CSF-cN apical extension. Using calcium imaging in crb1 and espin mutants, we further show that the size of the apical extension modulates the amplitude of CSF-cN sensory response to bending of the spinal cord. Based on our results, we propose that the apical actin ring could be a common site of initiation of actin-based protrusions in microvilliated sensory cells. Furthermore, our work provides a set of actors underlying actin-based protrusion elongation shared by different sensory cell types and highlights the critical role of the apical extension shape in sensory detection