Optic cup morphogenesis requires neural crest-mediated basement membrane assembly

Bryan, Chase D.; Casey, Macaulie A.; Pfeiffer, Rebecca L.; Jones, Bryan W.; Kwan, Kristen M.

doi:10.1242/dev.181420

Cited by 47 publications

(81 citation statements)

References 102 publications

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“…To visualize POM cells during in vivo time-lapse imaging, we used a sox10 cis regulatory element driving a membrane localized tdTomato (tg(sox10:lyntdTomato)). Sox10 is an established marker for the neural crest derived cells rather than for other mesenchymal cells of the POM [59][60][61]. We further crossed transgenic fish of this line to tg(hsp70:bmp4).…”

Section: Late Bmp Induction Results In Only Subtle Direct Changes Of mentioning

confidence: 99%

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP

Eckert

Knickmeyer

Heermann

2020

IJMS

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Colobomata, persistent optic fissures, frequently cause congenital blindness. Here, we focused on optic fissure fusion using in vivo time-lapse imaging in zebrafish. We identified the fusion initiating cells, which we termed “pioneer cells.” Based on morphology, localization, and downregulation of the neuroretinal (NR) precursor marker rx2, these cells could be considered as retinal pigment epithelial (RPE) progenitors. Notably, pioneer cells regain rx2 expression and integrate into the NR after fusion, indicating that they do not belong to the pool of RPE progenitors, supported by the lack of RPE marker expression in pioneer cells. They establish the first cellular contact between the margins in the proximal fissure region and separate the hyaloid artery and vein. After initiation, the fusion site is progressing distally, increasing the distance between the hyaloid artery and vein. A timed BMP (Bone Morphogenetic Protein) induction, resulting in coloboma, did not alter the morphology of the fissure margins, but it did affect the expression of NR and RPE markers within the margins. In addition, it resulted in a persisting basal lamina and persisting remnants of periocular mesenchyme and hyaloid vasculature within the fissure, supporting the necessity of BMP antagonism within the fissure margins. The hampered fissure fusion had severe effects on the vasculature of the eye.

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Section: Late Bmp Induction Results In Only Subtle Direct Changes Of mentioning

confidence: 99%

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP

Eckert

Knickmeyer

Heermann

2020

IJMS

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“…During ocular development, periocular neural crest cells migrate anteriorly to surround the evaginating optic vesicles (Bryan, Casey, Pfeiffer, Jones, & Kwan, 2020; Langenberg et al, 2008). After optic cup invagination, cranial neural crest cells migrate around the optic cup in two streams; cells originating from the diencephalon migrate dorsally over the eye cup, whereas cells from the anterior mesencephalon migrate ventrally around the eye cup and through the choroid fissure (Bohnsack & Kahana, 2013; Chawla, Schley, Williams, & Bohnsack, 2016).…”

Section: Neural Crestmentioning

confidence: 99%

“…The cellular functions of ocular neural crest cells have recently been elucidated. Periocular neural crest cells produce nidogen, a molecule that crosslinks laminin and is essential for basement membrane assembly within the choroid fissure (Bryan et al, 2020; Carrara, Weaver, Piedade, Vöcking, & Famulski, 2019; Mayer, Kohfeldt, & Timpl, 1998). Reduced nidogen production is observed in foxd3;tfap2a mutants, resulting aberrant ocular ECM assembly.…”

Section: Neural Crestmentioning

confidence: 99%

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Yoon

Fox

Dicipulo

et al. 2020

American J of Med Genetics Pt C

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Ocular coloboma is a congenital disorder of the eye where a gap exists in the inferior retina, lens, iris, or optic nerve tissue. With a prevalence of 2-19 per 100,000 live births, coloboma, and microphthalmia, an associated ocular disorder, represent up to 10% of childhood blindness. It manifests due to the failure of choroid fissure closure during eye development, and it is a part of a spectrum of ocular disorders that include microphthalmia and anophthalmia. Use of genetic approaches from classical pedigree analyses to next generation sequencing has identified more than 40 loci that are associated with the causality of ocular coloboma. As we have expanded studies to include singleton cases, hereditability has been very challenging to prove. As such, researchers over the past 20 years, have unraveled the complex interrelationship amongst these 40 genes using vertebrate model organisms. Such research has greatly increased our understanding of eye development. These genes function to regulate initial specification of the eye field, migration of retinal precursors, patterning of the retina, neural crest cell biology, and activity of head mesoderm. This review will discuss the discovery of loci using patient data, their investigations in animal models, and the recent advances stemming from animal models that shed new light in patient diagnosis.

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“…There is increasing evidence pointing to the importance of the periocular ECM in the morphogenesis of the optic cup, 31 with cross-linking of laminin, collagen IV, and other ECM components noted as critical factors. 32 In conditions associated with COL4A1 variants, eye abnormalities, including ASD, are the second commonest presenting feature. 33 COL4A1 forms a heterotrimer with COL4A2, and is secreted into the ECM to form a scaffolding, with key bonds to other heterotrimers.…”

Section: Variants In Collagen and Extracellular Matrix-associated Genmentioning

confidence: 99%

Revealing hidden genetic diagnoses in the ocular anterior segment disorders

Yousoof

Grigg

et al. 2020

Genetics in Medicine

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Purpose: Ocular anterior segment disorders (ASDs) are clinically and genetically heterogeneous, and genetic diagnosis often remains elusive. In this study, we demonstrate the value of a combined analysis protocol using phenotypic, genomic, and pedigree structure data to achieve a genetic conclusion. Methods: We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases. Results: We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6. Conclusions: We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously "hidden" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes.

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Optic cup morphogenesis requires neural crest-mediated basement membrane assembly

Cited by 47 publications

References 102 publications

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP

In Vivo Analysis of Optic Fissure Fusion in Zebrafish: Pioneer Cells, Basal Lamina, Hyaloid Vessels, and How Fissure Fusion is Affected by BMP

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Revealing hidden genetic diagnoses in the ocular anterior segment disorders

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