Chapter 41 Retinoic acid synthesis and breakdown in the developing mouse retina

Dräger, Ursula C.; Li, Huanchen; Wagner, Elisabeth; McCaffery, Peter

doi:10.1016/s0079-6123(01)31045-2

Cited by 12 publications

(14 citation statements)

References 42 publications

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“…The observed effect of excess RA on foxi1 expression might rather reveal a regulatory mechanism employed during other aspects of development. In zebrafish at 48 hpf, foxi1 is expressed in the retina, in the pharyngeal pouches and in the dorsal septum of the otic vesicle (Thisse et al, 2005), and RA signaling has been implicated in the development of all of these tissues (Drager et al, 2001;Mark et al, 2004;Romand, 2003). It is currently unknown, however, whether foxi1 expression depends on RA signaling in these tissues.…”

Section: Discussionmentioning

confidence: 99%

Changes in retinoic acid signaling alter otic patterning

Hans

Westerfield

2007

Development

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Retinoic acid (RA) has pleiotropic functions during embryogenesis. In zebrafish, increasing or blocking RA signaling results in enlarged or reduced otic vesicles, respectively. Here we elucidate the mechanisms that underlie these changes and show that they have origins in different tissues. Excess RA leads to ectopic foxi1 expression throughout the entire preplacodal domain. Foxi1 provides competence to adopt an otic fate. Subsequently, pax8, the expression of which depends upon Foxi1 and Fgf, is also expressed throughout the preplacodal domain. By contrast, loss of RA signaling does not affect foxi1 expression or otic competence, but instead results in delayed onset of fgf3 expression and impaired otic induction. fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos. Otic induction is rescued by fgf8 overexpression in RA-depleted embryos, although otic vesicles never achieve a normal size, suggesting that an additional factor is required to maintain otic fate. fgf3;tcf2 double mutants form otic vesicles similar to RA-signaling-depleted embryos, suggesting a signal from rhombomere 5-6 may also be required for otic fate maintenance. We show that rhombomere 5 wnt8b expression is absent in both RA-signaling-depleted embryos and in fgf3;tcf2 double mutants, and inactivation of wnt8b in fgf3 mutants by morpholino injection results in small otic vesicles, similar to RA depletion in wild type. Thus, excess RA expands otic competence, whereas the loss of RA impairs the expression of fgf3 and wnt8b in the hindbrain, compromising the induction and maintenance of otic fate.

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Section: Discussionmentioning

confidence: 99%

Changes in retinoic acid signaling alter otic patterning

Hans

Westerfield

2007

Development

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“…Less is known about RA signaling in the eye field region, although RAR receptors are widely distributed in early Xenopus embryos (Shiotsugu et al, 2004), RA synthesis has been detected in neurula stage Xenopus embryos (Ang and Duester, 1999b) and high levels of RA synthesis are present in the ventral retina at later stages of development (Drager et al, 2001). To investigate the regulation of RA synthesis during eye development, we screened for Raldh homologs, coding for retinaldehyde dehydrogenases, in Xenopus.…”

Section: Localization Of Hh Fgf and Ra Signaling Components Supportsmentioning

confidence: 99%

“…1A), suggesting that low Hh levels can at least partially ventralize the DR without concomitant expansion of the OS. RA has been suggested as an alternative signaling molecule that may control DV specification within the retina (Drager et al, 2001). RA treatments upregulated the OS marker Pax2 in zebrafish (Hyatt et al, 1996), while reduced RA signaling caused abnormal development of the VR in different animal models (Marsh-Armstrong et al, 1994;Ross et al, 2000), at least at the morphological level.…”

Section: Loss-of-function Experiments Suggest That Ventral Eye Specifmentioning

confidence: 99%

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Dorsoventral patterning of theXenopuseye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling

et al. 2005

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In the developing spinal cord and telencephalon, ventral patterning involves the interplay of Hedgehog (Hh), Retinoic Acid (RA) and Fibroblast Growth Factor (FGF) signaling. In the eye, ventral specification involves Hh signaling, but the roles of RA and FGF signaling are less clear. By overexpression assays in Xenopus embryos, we found that both RA and FGF receptor (FGFR) signaling ventralize the eye, by expanding optic stalk and ventral retina, and repressing dorsal retina character. Co-overexpression experiments show that RA and FGFR can collaborate with Hh signaling and reinforce its ventralizing activity. In loss-of-function experiments, a strong eye dorsalization was observed after triple inhibition of Hh, RA and FGFR signaling, while weaker effects were obtained by inhibiting only one or two of these pathways. These results suggest that the ventral regionalization of the eye is specified by interactions of Hh, RA and FGFR signaling. We argue that similar mechanisms might control ventral neural patterning throughout the central nervous system.

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“…Both gain-and loss-of-function studies have provided direct evidence that endogenous retinoids are required for appropriate specification and patterning of several tissues including the hindbrain (Maden et al, 1996;Gale et al, 1999;Dupé and Lumsden, 2001;Niederreither et al, 1997;Niederreither et al, 2000;Sirbu et al, 2005) (reviewed by Gavalas and Krumlauf, 2000;Maden, 2002), spinal cord (Sockanathan and Jessell, 1998;Pierani et al, 1999;Novitch et al, 2003;Diez del Corral et al, 2003;Wilson et al, 2004) (reviewed by Wilson and Maden, 2005), eye (Hyatt et al, 1996;Dickman et al, 1997;Wagner et al, 2000) (reviewed by Drager et al, 2001) and branchial arches (Maden et al, 1996;Niederreither et al, 1999;Niederreither et al, 2003;Quinlan et al, 2002) (reviewed by Mark et al, 2004). The ability of RA to exert its full range of effects relies upon its capacity to signal in both an autocrine and paracrine fashion and alter gene expression in the recipient cell.…”

Section: Introductionmentioning

confidence: 99%

RALDH-independent generation of retinoic acid during vertebrate embryogenesis by CYP1B1

et al. 2007

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Several independent lines of evidence have revealed an instructive role for retinoic acid (RA) signalling in the establishment of normal pattern and cellular specification of the vertebrate embryo. Molecular analyses have previously identified the major RA-synthesising (RALDH1-3) and RA-degrading(CYP26A-C1) enzymes as well as other components involved in RA processing(e.g. CRABP). Although the majority of the early effects of RA can be attributed to the activity of RALDH2, many other effects are suggestive of the presence of an as yet unidentified RA source. Here we describe the identification, expression, biochemistry and functional analysis of CYP1B1, a member of the cytochrome p450 family of mono-oxygenases, and provide evidence that it contributes to RA synthesis during embryonic patterning. We present in vitro biochemical data demonstrating that this enzyme can generate both all-trans-retinal (t-RAL) and all-trans-retinoic acid (t-RA) from the precursor all-trans-retinol(t-ROH), but unlike the CYP26s, CYP1B1 cannot degrade t-RA. In particular, we focussed on the capacity of CYP1B1 to regulate the molecular mechanisms associated with dorsoventral patterning of the neural tube and acquisition of motor neuron progenitor domain identity. Concordant with its sites of expression and biochemistry, data are presented demonstrating that CYP1B1 is capable of eliciting responses that are consistent with the production of RA. Taken together, we propose that these data provide strong support for CYP1B1 being one of the RALDH-independent components by which embryos direct RA-mediated patterning.

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Chapter 41 Retinoic acid synthesis and breakdown in the developing mouse retina

Cited by 12 publications

References 42 publications

Changes in retinoic acid signaling alter otic patterning

Changes in retinoic acid signaling alter otic patterning

Dorsoventral patterning of theXenopuseye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling

RALDH-independent generation of retinoic acid during vertebrate embryogenesis by CYP1B1

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