BMP signaling orchestrates photoreceptor specification in the zebrafish pineal gland in collaboration with Notch

Quillien, Aurélie; Blanco-Sánchez, Bernardo; Halluin, Caroline; Moore, John C.; Lawson, Nathan D.; Blader, Patrick; Cau, Elise

doi:10.1242/dev.060988

Cited by 25 publications

(49 citation statements)

References 47 publications

(74 reference statements)

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“…In addition, Notch and BMP signaling pathways can block myogenic differentiation of C2C12 cells by regulating the expression of Hey1 through a direct interaction between Smad1 and NICD (50). In the zebrafish pineal gland, BMP signaling is a competence factor for Notch signaling to efficiently activate its target gene expression (51), whereas in the regulation of the initial formation of the olfactory nerve BMP signaling negatively affects Notch signaling to achieve the balance between the two pathways (52). In these two cases, it remains unclear how the two pathways are integrated.…”

Section: Discussionmentioning

confidence: 99%

Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye

Zhou

Tanzie

Yan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The ciliary body (CB) of the mammalian eye is responsible for secreting aqueous humor to maintain intraocular pressure, which is elevated in the eyes of glaucoma patients. It contains a folded two-layered epithelial structure comprising the nonpigmented inner ciliary epithelium (ICE), the pigmented outer ciliary epithelium (OCE), and the underlying stroma. Although the CB has an important function in the eye, its morphogenesis remains poorly studied. In this study, we show that conditional inactivation of the Jagged 1 (Jag1)-Notch2 signaling pathway in the developing CB abolishes its morphogenesis. Notch2 is expressed in the OCE of the CB, whereas Jag1 is expressed in the ICE. Conditional inactivation of Jag1 in the ICE or Notch2 in the OCE disrupts CB morphogenesis, but neither affects the specification of the CB region. Notch2 signaling in the OCE is required for promoting cell proliferation and maintaining bone morphogenetic protein (BMP) signaling, both of which have been suggested to be important for CB morphogenesis. Although Notch and BMP signaling pathways are known to crosstalk via the interaction between their downstream transcriptional factors, this study suggests that Notch2 maintains BMP signaling in the OCE possibly by repressing expression of secreted BMP inhibitors. Based on our findings, we propose that Jag1-Notch2 signaling controls CB morphogenesis at least in part by regulating cell proliferation and BMP signaling.T he mammalian eye is composed of the anterior segment, the posterior retina and the vitreous. The anterior segment consists of cornea, lens, and ciliary body (CB), whereas the posterior retina contains six types of retinal neurons and Müller glial cells, which are organized into three distinct cell layers. The light passes through the cornea and is then focused by the lens and detected by photoreceptors in the retina. Both the aqueous humor anteriorly and the vitreous humor posteriorly function together to sustain intraocular pressure (IOP) in the eye and thereby maintain its shape. Pressure regulation is particularly important because abnormally high IOP is a major risk factor for glaucoma (1). In the eye, the CB is responsible for producing aqueous humor (2). Although high IOP is often attributed to the blockage of the drainage system for the vitreous, known as the trabecular meshwork, abnormal CB function might also contribute to high IOP formation because of excess aqueous humor production. Finally, contraction of the muscles in the CB controls lens accommodation for near versus far vision. Despite its important biological functions and potential medical significance, the formation and development of the CB remain poorly studied.The CB contains two layers of apically adhered epithelial sheets, the pigmented outer ciliary epithelium (OCE) and the nonpigmented inner ciliary epithelium (ICE), and the underlying stroma (2). It forms at the periphery of the developing optic cup and first segregates from the retina and then from the iris. One previous study suggested that blood vesse...

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Section: Discussionmentioning

confidence: 99%

Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye

Zhou

Tanzie

Yan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Although we have learned a great deal concerning the role of Notch in vascular development from genetic manipulations in model systems, we still know little about when and where Notch is activated in endothelial cells during embryogenesis. We previously generated zebrafish lines that allow visualization of Notch-responsive cells and lineage tracing of progeny cells in which Notch has been activated (Clements et al, 2011;Lorent et al, 2010;Parsons et al, 2009;Quillien et al, 2011;Wang et al, 2011). In the study reported here, we have applied these transgenic lines together with genetic manipulation of Notch receptors and ligands, to investigate the dynamic role of Notch signaling during vascular development.…”

Section: Introductionmentioning

confidence: 99%

Distinct Notch signaling outputs pattern the developing arterial system

et al. 2014

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Differentiation of arteries and veins is essential for the development of a functional circulatory system. In vertebrate embryos, genetic manipulation of Notch signaling has demonstrated the importance of this pathway in driving artery endothelial cell differentiation. However, when and where Notch activation occurs to affect endothelial cell fate is less clear. Using transgenic zebrafish bearing a Notch-responsive reporter, we demonstrate that Notch is activated in endothelial progenitors during vasculogenesis prior to blood vessel morphogenesis and is maintained in arterial endothelial cells throughout larval stages. Furthermore, we find that endothelial progenitors in which Notch is activated are committed to a dorsal aorta fate. Interestingly, some arterial endothelial cells subsequently downregulate Notch signaling and then contribute to veins during vascular remodeling. Lineage analysis, together with perturbation of both Notch receptor and ligand function, further suggests several distinct developmental windows in which Notch signaling acts to promote artery commitment and maintenance. Together, these findings demonstrate that Notch acts in distinct contexts to initiate and maintain artery identity during embryogenesis.

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“…Although an increasing body of work has characterized the development of the pineal organ and the habenular nuclei in zebrafish (Masai et al, 1997;Cau and Wilson, 2003;Cau et al, 2008;Quillien et al, 2011), comparatively little attention has been lent to the formation of parapineal neurons. Previous work suggests that parapineal cells are likely to be specified prior to the 15-somite stage from a group of precursors in the anterior pineal complex anlage (Masai et al, 1997;Snelson et al, 2008a).…”

Section: Introductionmentioning

confidence: 99%

“…All pineal complex cell types undergo their final mitotic division in a similar time period between 15 and 24 hpf (Cau et al, 2008;Snelson et al, 2008b). The generation of the proper numbers of the different cell types (parapineal, pineal rod photoreceptor, pineal cone photoreceptor and pineal projection neuron) from the pineal complex anlage requires input from the Notch and Bmp pathways as well as the activity of at least two different transcription factors, T-box containing transcription factor 2b (Tbx2b) and the homeodomain-containing protein Floating head (Flh) (Masai et al, 1997;Cau et al, 2008;Snelson et al, 2008a;Snelson et al, 2008b;Quillien et al, 2011). However, additional genes are likely to be involved in cell specification in the pineal complex anlage, as a small number of parapineal and pineal neurons do form in tbx2b; flh double mutants (Snelson et al, 2008a).…”

Section: Introductionmentioning

confidence: 99%

Fgf signaling governs cell fate in the zebrafish pineal complex

2013

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SUMMARYLeft-right (L-R) asymmetries in neuroanatomy exist throughout the animal kingdom, with implications for function and behavior. The molecular mechanisms that control formation of such asymmetries are beginning to be understood. Significant progress has been made by studying the zebrafish parapineal organ, a group of neurons on the left side of the epithalamus. Parapineal cells arise from the medially located pineal complex anlage and migrate to the left side of the brain. We have found that Fgf8a regulates a fate decision among anterior pineal complex progenitors that occurs just prior to the initiation of leftward migration. Cell fate analysis shows that in the absence of Fgf8a a subset of cells in the anterior pineal complex anlage differentiate as cone photoreceptors rather than parapineal neurons. Fgf8a acts permissively to promote parapineal fate in conjunction with the transcription factor Tbx2b, but might also block cone photoreceptor fate. We conclude that this subset of anterior pineal complex precursors, which normally become parapineal cells, are bipotential and require Fgf8a to maintain parapineal identity and/or prevent cone identity.

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BMP signaling orchestrates photoreceptor specification in the zebrafish pineal gland in collaboration with Notch

Cited by 25 publications

References 47 publications

Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye

Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye

Distinct Notch signaling outputs pattern the developing arterial system

Fgf signaling governs cell fate in the zebrafish pineal complex

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