Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression

Sehgal, Rachna; Karcavich, Rachel E.; Carlson, Scott M.; Belecky-Adams, Teri L.

doi:10.1016/j.ydbio.2008.03.041

Cited by 29 publications

(42 citation statements)

References 68 publications

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“…2h). Similar results were obtained when Pax6 was blocked or Pax2 was overexpressed in early stage 10 chick embryos (Canto-Soler and Adler, 2006; Sehgal et al, 2008). We also observed some embryos in which the eyes with ventral defects also had smaller lenses (Fig.…”

Section: Resultssupporting

confidence: 80%

Complement component C3aR constitutes a novel regulator for chick eye morphogenesis

Grajales-Esquivel

Luz-Madrigal

Bierly

et al. 2017

Developmental Biology

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Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina. We show by immunofluorescence staining that C3 and the receptor for C3a (the cleaved and active form of C3), C3aR, are present in chick embryos during eye morphogenesis in the OV and OC. Interestingly, C3aR is mainly localized in the nuclear compartment at the OC stage. Loss of function studies at the OV stage using morpholinos or a blocking antibody targeting the C3aR (anti-C3aR Ab), causes eye defects such as microphthalmia and defects in the ventral portion of the eye that result in coloboma. Such defects were not observed when C3aR was disrupted at the OC stage. Histological analysis demonstrated that microphthalmic eyes were unable to generate a normal optic stalk or a closed OC. The dorsal/ventral patterning defects were accompanied by an expansion of the ventral markers Pax2, cVax and retinoic acid synthesizing enzyme raldh-3 (aldh1a3) domains, an absence of the dorsal expression of Tbx5 and raldh-1 (aldh1a1) and a re-specification of the ventral RPE to neuroepithelium. In addition, the eyes showed overall decreased expression of Gli1 and a change in distribution of nuclear β-catenin, suggesting that Shh and Wnt pathways have been affected. Finally, we observed prominent cell death along with a decrease in proliferating cells, indicating that both processes contribute to the microphthalmic phenotype. Together our results show that C3aR is necessary for the proper morphogenesis of the OC. This is the first report implicating C3aR in eye development, revealing an unsuspected hitherto regulator for proper chick eye morphogenesis.

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Section: Resultssupporting

confidence: 80%

Complement component C3aR constitutes a novel regulator for chick eye morphogenesis

Grajales-Esquivel

Luz-Madrigal

Bierly

et al. 2017

Developmental Biology

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“…This correlation suggests that Pax2 may suppress the de-differentiation of Müller glia or promote glial phenotype in central regions of the retina. Consistent with this notion, Pax2 is known to promote glial phenotypes in the developing optic nerve [90][91][92]. Pax2 may inhibit the acquisition of neuronal phenotypes by suppressing the expression of pro-neural genes and by inhibiting the expression of Pax6, which promotes the multipotency of retinal progenitors (reviewed by [93]).…”

Section: Mapk Signaling and The De-differentiation And Proliferation mentioning

confidence: 88%

Turning Müller Glia into Neural Progenitors in the Retina

Fischer

Bongini

2010

Mol Neurobiol

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Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Müller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Müller glia-derived progenitors, with emphasis on findings in the chick retina. The Müller glia are a promising source of regeneration-supporting cells that are intrinsic to the retina and significant evidence indicated these glias can be stimulated to produce neurons in different classes of vertebrates. The key to harnessing the neurogenic potential of Müller glia is to identify the secreted factors, signaling pathways, and transcription factors that enable de-differentiation, proliferation, and neurogenesis. We review findings regarding the roles of mitogen-activated protein kinase and notch signaling in the proliferation and generation of Müller glia-derived retinal progenitors.

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“…Toward this end, we have discovered that nlz1 or nlz2 knockdown in zebrafish affects transcription of pax2.1, a key determinant of optic fissure and stalk identity. Pax2 null mice have been reported to have fissure closure defects (32) and overexpression of pax2.1 in zebrafish and chick has also been shown to cause coloboma and other eye abnormalities (33,34). The fact that pax2.1 expression is strongly inhibited in nlz1 morphants suggests that nlz1 likely acts as a transcriptional activator of pax2.1 in vivo.…”

Section: Nlz Proteins May Act In a Pax2-dependent Manner In The Ventrmentioning

confidence: 99%

Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure

Brown

Dutta

Bharti

et al. 2009

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

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The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. Here, we profile global gene expression during optic fissure closure using laser capture microdissected (LCM) tissue from the margins of the fissure. From these data, we identify a unique role for the C 2H2 zinc finger proteins Nlz1 and Nlz2 in normal fissure closure. Gene knockdown of nlz1 and/or nlz2 in zebrafish leads to a failure of the optic fissure to close, a phenotype which closely resembles that seen in human uveal coloboma. We also identify misregulation of pax2 in the developing eye of morphant fish, suggesting that Nlz1 and Nlz2 act upstream of the Pax2 pathway in directing proper closure of the optic fissure.coloboma ͉ eye ͉ pax2 ͉ zinc finger protein ͉ zebrafish T he mammalian eye begins as an evagination of forebrain neuroepithelium, the optic vesicle. As the optic vesicle approaches the surface ectoderm, it invaginates upon itself, forming a double-layered optic cup attached to the brain via the optic stalk. The asymmetric nature of this invagination leads to the formation of a gap along the ventral optic cup and optic stalk (the optic fissure) that remains open for hours to days, depending on the species. To form a spherical globe the margins of the optic fissure must meet and fuse ventrally during the 5th-7th

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Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression

Cited by 29 publications

References 68 publications

Complement component C3aR constitutes a novel regulator for chick eye morphogenesis

Complement component C3aR constitutes a novel regulator for chick eye morphogenesis

Turning Müller Glia into Neural Progenitors in the Retina

Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure

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