Regulation of retinal axon growth by secreted Vax1 homeodomain protein

Kim, Nam Suk; Min, Kwang Wook; Kang, Kyung‐Hwa; Lee, Eun Jung; Kim, Hyoung Tai; Moon, Kyunghwan; Choi, Jeong‐Yoon; Dai, Le; Lee, Sang‐Hee; Kim, Jin Woo

doi:10.7554/elife.02671

Cited by 29 publications

(63 citation statements)

References 48 publications

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“…Mice lacking Vax1 died perinatally, although some survived after birth (Bertuzzi et al 1999;Hallonet et al 1999), exhibiting cleft palate and coloboma due to the failure of optic fissure closure. In addition, these animals were unable to develop the optic chiasm and presented with axon guidance defects in the form of retinal ganglion cells whose axons were unable to properly localize within the brain (Kim et al 2014). Kim et al (2014) suggested that, in addition to its function as a transcription factor, Vax1 may also work as a secreted protein to promote the growth of retinal ganglion cells towards the brain.…”

Section: Vax1 (Ventral Anterior Homeobox 1)mentioning

confidence: 99%

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia

et al. 2019

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Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counselling challenging. In this review, we present the main genes implicated in nonsyndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients.

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Section: Vax1 (Ventral Anterior Homeobox 1)mentioning

confidence: 99%

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia

et al. 2019

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“…This classical role of homeodomain transcription factors has been challenged by the fact that homeoproteins can also act non-cell-autonomously by a mechanism involving secretion and intracellular transfer into neighboring cells (Prochiantz and Di Nardo, 2015). Recently, these disparate results were confirmed: Vax1 is secreted by ventral hypothalamic cells and binds to a heparan sulfate proteoglycan (HSPG) expressed on retinal axons and is internalized into retinal growth cones where it activates locally protein synthesis to promote axonal growth (Kim et al, 2014) (Fig. 1).…”

Section: Molecular Cues For Axon Growthmentioning

confidence: 99%

Retinal axon guidance at the midline: Chiasmatic misrouting and consequences

Prieur

Rebsam

2017

Developmental Neurobiology

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The visual representation of the outside world relies on the appropriate connectivity between the eyes and the brain. Retinal ganglion cells are the sole neurons that send an axon from the retina to the brain, and thus the guidance decisions of retinal axons en route to their targets in the brain shape the neural circuitry that forms the basis of vision. Here, we focus on the choice made by retinal axons to cross or avoid the midline at the optic chiasm. This decision allows each brain hemisphere to receive inputs from both eyes corresponding to the same visual hemifield, and is thus crucial for binocular vision. In achiasmatic conditions, all retinal axons from one eye project to the ipsilateral brain hemisphere. In albinism, abnormal guidance of retinal axons at the optic chiasm leads to a change in the ratio of contralateral and ipsilateral projections with the consequence that each brain hemisphere receives inputs primarily from the contralateral eye instead of an almost equal distribution from both eyes in humans. In both cases, this misrouting of retinal axons leads to reduced visual acuity and poor depth perception. While this defect has been known for decades, mouse genetics have led to a better understanding of the molecular mechanisms at play in retinal axon guidance and at the origin of the guidance defect in albinism. In addition, fMRI studies on humans have now confirmed the anatomical and functional consequences of axonal misrouting at the chiasm that were previously only assumed from animal models. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 844-860, 2017.

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“…VAX1 contains four exons and encodes a protein with DNA-binding paired-type homeodomain [272]. Vax1 protein can be secreted and penetrate into axons of RGC and other neurons [273].…”

Section: Vax1mentioning

confidence: 99%

“…In Danio rerio, Vax1 is expressed in the ventral portion of the developing eye [277]. It was discovered that Vax1 is secreted from ventral hypothalamic cells and diffuses to RGC axons, where it promotes axonal growth [273]. Microphthalmia associated with cleft lip and palate and agenesis of the corpus callosum caused by homozygous mutation in the Vax1 gene was reported [278].…”

Section: Vax1mentioning

confidence: 99%

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

Markitantova

Симирский

2020

IJMS

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Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina.

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Regulation of retinal axon growth by secreted Vax1 homeodomain protein

Cited by 29 publications

References 48 publications

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia

Retinal axon guidance at the midline: Chiasmatic misrouting and consequences

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

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