Serotonin Signaling Is Required for Wnt-Dependent GRP Specification and Leftward Flow in Xenopus

Beyer, Tina; Danilchik, Michael V.; Thumberger, Thomas; Vick, Philipp; Tisler, Matthias; Schneider, Isabelle; Bogusch, Susanne; André, Philipp; Ulmer, Bärbel; Walentek, Peter; Niesler, Beate; Blum, Martin; Schweickert, Axel

doi:10.1016/j.cub.2011.11.027

Cited by 62 publications

(86 citation statements)

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“…For example, ATP4 was shown to be symmetrically expressed in frog embryos and to control ciliogenesis and cilia polarization (Walentek et al, 2012). Serotonin was also found in a symmetrical fashion and was shown to be required for specification of the LRO precursor in the frog, the so-called superficial mesoderm (Beyer et al, 2012a). Finally, gap junction communication has been implicated in the transfer of asymmetric cue(s) from the LRO to the left LPM in frog and mouse (Beyer et al, 2012b;Saund et al, 2012;Viotti et al, 2012).…”

Section: Lr Patterning During Vertebrate Evolutionmentioning

confidence: 99%

The evolution and conservation of left-right patterning mechanisms

et al. 2014

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Morphological asymmetry is a common feature of animal body plans, from shell coiling in snails to organ placement in humans. The signaling protein Nodal is key for determining this laterality. Many vertebrates, including humans, use cilia for breaking symmetry during embryonic development: rotating cilia produce a leftward flow of extracellular fluids that induces the asymmetric expression of Nodal. By contrast, Nodal asymmetry can be induced flow-independently in invertebrates. Here, we ask when and why flow evolved. We propose that flow was present at the base of the deuterostomes and that it is required to maintain organ asymmetry in otherwise perfectly bilaterally symmetrical vertebrates.

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Section: Lr Patterning During Vertebrate Evolutionmentioning

confidence: 99%

The evolution and conservation of left-right patterning mechanisms

et al. 2014

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“…4B). We recently demonstrated a role for Htr3 in Wnt/β-catenin dependent expression of foxj1 during blastula/gastrula stages (Beyer et al, 2012). As foxj1 induces motile cilia in epidermal MCCs as well (Stubbs et al, 2008), we wondered whether Htr3 might be required for foxj1 expression in the skin.…”

Section: Sscs Synthesize Serotonin In the Larval Skinmentioning

confidence: 99%

“…The serotonin effect on motile cilia, which are used to move individual cells, whole organisms or extracellular fluids such as mucus and cerebrospinal fluid, can be twofold, via the induction of ciliogenesis or by regulation of ciliary beat frequency (CBF). During left-right axis determination in Xenopus, serotonin signaling induces foxj1 in a Wnt/β-catenin dependent manner (Beyer et al, 2012). foxj1 in turn governs the formation of motile cilia (Stubbs et al, 2008;Yu et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles

et al. 2014

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The embryonic skin of Xenopus tadpoles serves as an experimental model system for mucociliary epithelia (MCE) such as the human airway epithelium. MCEs are characterized by the presence of mucus-secreting goblet and multiciliated cells (MCCs). A third cell type, ion-secreting cells (ISCs), is present in the larval skin as well. Synchronized beating of MCC cilia is required for directional transport of mucus. Here we describe a novel cell type in the Xenopus laevis larval epidermis, characterized by serotonin synthesis and secretion. It is termed small secretory cell (SSC). SSCs are detectable at early tadpole stages, unlike MCCs and ISCs, which are specified at early neurulation. Subcellularly, serotonin was found in large, apically localized vesicle-like structures, which were entirely shed into the surrounding medium. Pharmacological inhibition of serotonin synthesis decreased the velocity of cilia-driven fluid flow across the skin epithelium. This effect was mediated by serotonin type 3 receptor (Htr3), which was expressed in ciliated cells. Knockdown of Htr3 compromised flow velocity by reducing the ciliary motility of MCCs. SSCs thus represent a distinct and novel entity of the frog tadpole MCE, required for ciliary beating and mucus transport across the larval skin. The identification and characterization of SSCs consolidates the value of the Xenopus embryonic skin as a model system for human MCEs, which have been known for serotonindependent regulation of ciliary beat frequency.

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“…In mice uptake of 5-HT during early development is first observed in non-neural tissues such as the heart, the liver, the cranial mesenchyme, the migrating cranial neural crest cells (NCCs), dorsal ganglia and retinal ganglion cells (Lauder and Zimmerman, 1988; Narboux-Nème et al, 2008). High affinity uptake of 5-HT in these structures highlights the involvement of 5-HT signaling in their development and suggests that 5-HT must be finely modulated.So far evidence has been presented for 5-HT involvement in the establishment of left-right asymmetry, the craniofacial, limb, bone and heart development, the closure of the neural tube and neuronal differentiation during early neurogenesis (Whitaker-Azmitia, 2001;Levin et al, 2006;Beyer et al, 2012;Vandenberg et al, 2013). In mice 5-HT has been found to influence the development of the whisker-barrel fields in the somatosensory cortex and the thalamocortical axon guidance, suggesting that dysfunction of 5-HT signaling during development may alter brain circuitry and functioning (Cases et al, 1996;Persico et al, 2001;Bonnin et al, 2007).…”

mentioning

confidence: 99%

“…So far evidence has been presented for 5-HT involvement in the establishment of left-right asymmetry, the craniofacial, limb, bone and heart development, the closure of the neural tube and neuronal differentiation during early neurogenesis (Whitaker-Azmitia, 2001;Levin et al, 2006;Beyer et al, 2012;Vandenberg et al, 2013). In mice 5-HT has been found to influence the development of the whisker-barrel fields in the somatosensory cortex and the thalamocortical axon guidance, suggesting that dysfunction of 5-HT signaling during development may alter brain circuitry and functioning (Cases et al, 1996;Persico et al, 2001;Bonnin et al, 2007).…”

mentioning

confidence: 99%

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

Ori¹,

Lucchini²,

Marras³

et al. 2013

Int. J. Dev. Biol.

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The serotonin receptor 5-HT2B has been shown to be critically important during embryogenesis as the knockout of this gene in mice causes heart defects and embryonic lethality that impairs further analyses on other embryonic cell and tissue types. In the present review, we highlight how the use of Xenopus laevis, an alternative vertebrate model suitable for gene loss and gain of function analyses, has contributed to our understanding of the role of 5-HT2B signaling during development. In vivo studies showed that 5-HT2B signaling is not only required for heart development, but that it also has a crucial role in ocular and craniofacial morphogenesis, being involved in shaping the first branchial arch and the jaw joint, in retinogenesis and possibly in periocular mesenchyme development. These findings may be relevant for our understanding of congenital defects including human birth malformations. In addition, 5-HT2B appears to be required for the therapeutic actions of selective serotonin reuptake inhibitors commonly prescribed as antidepressant drugs to pregnant and lactating women. We discuss how the understanding of the molecular basis of serotonin signaling in a suitable animal embryogenesis model may open new lines of investigations and therapies in humans. KEY WORDS: 5-HT2B, neural crest cell, eye, craniofacial morphogenesis, SSRISerotonin, an ancient molecule with unsuspected and still unveiled functions Serotonin (5-hydroxytryptamine, 5-HT) is a phylogenetically ancient monoamine that fulfills a broad role in the control of many vital functions including the control of gastrointestinal motility and secretion, cardiovascular regulation, hemostatic processes, the regulation of circadian rhythms, the control of the sleep-wake cycle, memory and learning, perception of pain, appetite and sexual behavior (reviewed by Berger et al., 2009). The broad action of the serotonin signaling system has attracted the interest of researchers in various fields of biology and molecular medicine, spanning from developmental biology, neurobiology to molecular psychiatry. 5-HT is best known for its role in the nervous system where it is one of the neurotransmitters mainly involved in the etiology of various human psychiatric disorders, including anxiety, depression, obsessive-compulsive disorders, schizophrenia, pain and migraine. Accordingly, many substances that interfere with the serotonergic system are commonly used as therapeutic agents. Selective serotonin reuptake inhibitors (SSRIs) are, in fact, the most frequently prescribed drugs for the treatment of depression Int. J. Dev. Biol. 57: 707-714 (2013) Abbreviations used in this paper: 5-HT, serotonin; 5-HTT, serotonin transporter; CNS, central nervous system; CMZ, ciliary marginal zone; Edn1, endothelin 1; GCL, gaglion cell layer; INL, inner nuclear layer; NCCs, neural crest cells; POM, periocular mesenchyme; SSRI, selective serotonin reuptake inhibitors; Tph2, tryptophan hydroxylase 2.and anxiety-related disorders (Berton and Nestler, 2006). These drugs inhibit...

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Serotonin Signaling Is Required for Wnt-Dependent GRP Specification and Leftward Flow in Xenopus

Cited by 62 publications

References 44 publications

The evolution and conservation of left-right patterning mechanisms

The evolution and conservation of left-right patterning mechanisms

A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

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