Lunatic fringe causes expansion and increased neurogenesis of trunk neural tube and neural crest populations

Bellard, María Elena de; Barembaum, Meyer; Arman, Odette; Bronner‐Fraser, Marianne

doi:10.1017/s1740925x07000683

Cited by 10 publications

(9 citation statements)

References 45 publications

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“…One possibility is that the milder neurogenic effect of lfng knockdown cannot be detected for reticulospinal neurons due to their low number, or there may be differences in the regulation of their differentiation compared with subsequent neurogenesis. Our findings appear contrary to a study in which retroviralmediated overexpression of Lfng in the chick neural tube increases the number of neurons (de Bellard et al, 2007), as we found that transgenic expression of Lfng in r3/r5 decreases neurogenesis. One contributory factor is suggested by our observation that widespread knockdown of lfng has less of an effect on neurogenesis than occurs cell autonomously for mosaic knockdown, consistent with the competition to differentiate during the lateral inhibition of neurogenesis.…”

Section: Notch In the Lateral Inhibition Of Neurogenesiscontrasting

confidence: 99%

“…Furthermore, overexpression of Lfng in the chick neural tube was found to increase the number of neurons (de Bellard et al, 2007). These findings raise the possibility that modulation of Notch activity by Fringe homologues regulates neurogenesis in vertebrates.…”

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confidence: 81%

“…It is therefore intriguing that specific Fringe homologues are expressed in the vertebrate CNS; for example, Lfng expression occurs in dorsoventral stripes in the chick and mouse neural tube (Johnston et al, 1997;Laufer et al, 1997) that could correlate with neurogenesis, and Fringe homologues are expressed in progenitors and Lunatic fringe promotes the lateral inhibition of neurogenesis differentiating cells in the cerebral cortex in mouse (Ishii et al, 2000). Furthermore, overexpression of Lfng in the chick neural tube was found to increase the number of neurons (de Bellard et al, 2007). These findings raise the possibility that modulation of Notch activity by Fringe homologues regulates neurogenesis in vertebrates.…”

Section: Introductionmentioning

confidence: 99%

“…This can explain our finding that widespread transgenic overexpression of Lfng within r3/r5 inhibits neurogenesis only to a modest extent. A potential explanation for increased neurogenesis in the chick neural tube is suggested by the major increase in cell proliferation that occurs following Lfng expression (de Bellard et al, 2007). Since effects on neuronal differentiation were analysed 24-48 hours after retroviral infection, expansion of the progenitor pool may underlie the increased number of neurons and outweigh a modest inhibition of differentiation by widespread Lfng expression.…”

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confidence: 99%

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Lunatic fringe promotes the lateral inhibition of neurogenesis

Nikolaou¹,

Watanabe-Asaka²,

Gerety³

et al. 2009

Development

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Previous studies have identified roles of the modulation of Notch activation by Fringe homologues in boundary formation and in regulating the differentiation of vertebrate thymocytes and Drosophila glial cells. We have investigated the role of Lunatic fringe (Lfng) expression during neurogenesis in the vertebrate neural tube. We find that in the zebrafish hindbrain, Lfng is expressed by progenitors in neurogenic regions and downregulated in cells that have initiated neuronal differentiation. Lfng is required cell autonomously in neural epithelial cells to limit the amount of neurogenesis and to maintain progenitors. By contrast, Lfng is not required for the role of Notch in interneuronal fate choice, which we show is mediated by Notch1a. The expression of Lfng does not require Notch activity, but rather is regulated downstream of proneural genes that are widely expressed by neural progenitors. These findings suggest that Lfng acts in a feedback loop downstream of proneural genes, which, by promoting Notch activation, maintains the sensitivity of progenitors to lateral inhibition and thus limits further proneural upregulation.KEY WORDS: Lateral inhibition, Neurogenesis, Neural progenitors, Notch, Fringe, Zebrafish Development 136, 2523Development 136, -2533Development 136, (2009 DEVELOPMENT 2524 differentiating cells in the cerebral cortex in mouse (Ishii et al., 2000). Furthermore, overexpression of Lfng in the chick neural tube was found to increase the number of neurons (de Bellard et al., 2007). These findings raise the possibility that modulation of Notch activity by Fringe homologues regulates neurogenesis in vertebrates.We set out to investigate the role of Lfng in the zebrafish nervous system, in which gene expression studies have suggested potential roles in boundary formation and/or neurogenesis. At early stages, lfng expression occurs at high levels in alternating segments in the hindbrain (Leve et al., 2001;Prince et al., 2001;Qiu et al., 2004), which by analogy with roles in other tissues could underlie boundary formation. In addition, lfng is expressed in dorsoventrally restricted domains in the neural tube (Prince et al., 2001) that could be associated with zones of neurogenesis. We show that Lfng limits neuronal differentiation and is required to maintain progenitor cells. Lfng acts cell autonomously in progenitors to inhibit their differentiation but, surprisingly, is upregulated downstream of proneural genes. We propose that Lfng acts in a feedback loop that maintains the competence of progenitor cells to receive lateral inhibition from differentiating neurons. MATERIALS AND METHODS Zebrafish linesWild-type, mib ta52b Schier et al., 1996), notch1a tp37 (Gray et al., 2001;Holley et al., 2002;van Eeden et al., 1996) and Tg(r3/r5-Gal4::UAS-RFP) embryos were produced and staged according to hours post fertilisation (hpf) and morphological criteria (Kimmel et al., 1995). MicroinjectionBlastomeres (1-to 4-cell) were microinjected with 0.45-1.8 pmol morpholino oligonucleotide (MO; Gene Tools). The ...

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Section: Notch In the Lateral Inhibition Of Neurogenesiscontrasting

confidence: 99%

mentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Lunatic fringe promotes the lateral inhibition of neurogenesis

Nikolaou¹,

Watanabe-Asaka²,

Gerety³

et al. 2009

Development

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“…Both loss-of-function of lfng in zebrafish and Notch1 in mice leads to an early increase in the number of differentiating neurons leading to a reduction in the size of brain structures as a result of secondary progenitor pool depletion [Lutolf et al, 2002;Yoon and Gaiano, 2005;Nikolaou et al, 2009], while overexpression results in an increase of neuronal progenitor cells at the expense of differentiating cells [Gaiano et al, 2000;Breunig et al, 2007;Li et al, 2008;Nikolaou et al, 2009;Kato et al, 2010]. The latter may in turn result in an enlargement of brain structures [de Bellard et al, 2007]. Interestingly, ASDs are associated with an enlarged brain volume (and head circumference) [Kanner, 1943;Piven et al, 1995;Woodhouse et al, 1996].…”

Section: Discussionmentioning

confidence: 99%

A 380-kb Duplication in 7p22.3 Encompassing the <b><i>LFNG</i></b> Gene in a Boy with Asperger Syndrome

et al. 2011

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De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH signaling. We suggest that this copy number variation has been a contributive factor to the occurrence of Asperger syndrome in this patient.

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New methods for chicken embryo manipulations

El-Ghali

Rabadi

Ezin

et al. 2009

Microscopy Res & Technique

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The capacity to image a growing embryo while simultaneously studying the developmental function of specific molecules provides invaluable information on embryogenesis. However, until recently, this approach was accomplished with difficulty both because of the advanced technology needed and because an easy method of minimizing damage to the embryo was unavailable. Here we present a novel way of adapting the well-known EC culture of whole chick embryos to time-lapse imaging and to functional molecular studies using blocking agents. The novelty of our method stems from the ability to apply blocking agents ex ovo as well as in ovo. We were able to study the function of a set of molecules by culturing developing embryos ex ovo in tissue culture media containing these molecules or by injecting them underneath the live embryo in ovo. The in ovo preparation is particularly valuable since it extends the period of time during which the developmental function of the molecule can be studied and it provides an easy, reproducible method for screening a batch of molecules. These new techniques will prove very helpful in visualizing and understanding the role of specific molecules during embryonic morphogenesis, including blood vessel formation.

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Lunatic fringe causes expansion and increased neurogenesis of trunk neural tube and neural crest populations

Cited by 10 publications

References 45 publications

Lunatic fringe promotes the lateral inhibition of neurogenesis

Lunatic fringe promotes the lateral inhibition of neurogenesis

A 380-kb Duplication in 7p22.3 Encompassing the <b><i>LFNG</i></b> Gene in a Boy with Asperger Syndrome

New methods for chicken embryo manipulations

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