Lens differentiation and crystallin regulation: a chick model

Reza, Hasan Mahmud; Yasuda, Kazuaki

doi:10.1387/ijdb.041863hr

Cited by 35 publications

(24 citation statements)

References 117 publications

(149 reference statements)

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“…The expression of crystallin genes is regulated by the combinatorial activities of several different transcription factors, including Pax6 and Sox2 [40-42,47-49]. The pax6 gene was previously shown to be downregulated in the cavefish lens [7,32], and this result was confirmed here (data not shown).…”

Section: Resultssupporting

confidence: 86%

“…Sox2 generally exhibits gene regulatory functions by forming complexes with partner transcription factors, and the binding of a single Sox protein alone to a DNA site does not lead to transcriptional activation or repression [38,39]. In many species, Pax6 and Sox2 regulate crystallin gene expression cooperatively [40,41]. For example, Sox2 has been shown to bind cooperatively with Pax6 to the δ-crystallin minimal enhancer DC5 [42].…”

Section: Introductionmentioning

confidence: 99%

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The role of a lens survival pathway including sox2 and αA-crystallin in the evolution of cavefish eye degeneration

Parkhurst

Jeffery

2014

EvoDevo

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BackgroundThe teleost Astyanax mexicanus is a single species consisting of eyed surface-dwelling (surface fish) and blind cave-dwelling (cavefish) morphs. Cavefish eyes are lost through apoptosis of the lens, which in turn promotes the degeneration of other optic tissues. The αA-crystallin (αA-crys) gene is strongly downregulated in the cavefish lens and is located in a genomic region (QTL) responsible for eye loss. Therefore, αA-crys has been proposed as a candidate for regulating cavefish eye degeneration. The purpose of this study was to determine the mechanism of αA-crys downregulation and its role in cavefish eye degeneration.ResultsThe involvement of αA-crys in eye degeneration was confirmed by knocking down its expression in surface fish, which led to apoptosis of the lens. The underlying reason for αA-crys downregulation in cavefish was investigated by comparing genomic αA-crys DNA sequences in surface fish and cavefish, however, no obvious cis-regulatory factors were discovered. Furthermore, the cavefish αA-crys allele is expressed in surface fish x cavefish F1 hybrids, indicating that evolutionary changes in upstream genes are most likely responsible for αA-crys downregulation. In other species, Sox2 is one of the transcription factors that regulate lens crystallin genes during eye development. Determination of sox2 expression patterns during surface fish and cavefish development showed that sox2 is specifically downregulated in the cavefish lens. The upstream regulatory function of Sox2 was demonstrated by knockdown in surface fish, which abolished αA-crys expression and induced lens apoptosis.ConclusionsThe results suggest that αA-crys is required for normal eye development in cavefish via suppression of lens apoptosis. The regulatory changes involved in αA-crys downregulation in cavefish are in trans-acting factors rather than cis-acting mutations in the αA-crys gene. Therefore, αA-crys is unlikely to be the mutated gene(s) associated with an Astyanax eye QTL. The results reveal a genetic pathway leading from sox2 to αA-crys that is required for survival of the lens in Astyanax surface fish. Defects in this pathway may be involved in lens apoptosis and thus a cause of cavefish eye degeneration.

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Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The role of a lens survival pathway including sox2 and αA-crystallin in the evolution of cavefish eye degeneration

Parkhurst

Jeffery

2014

EvoDevo

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“…Both in SF and in CF, the lens epithelium proliferates continuously; its posterior cells exit the cell cycle and transform into primary fibers in the case of SF or undergo massive cell death in the case of CF (for a recent review on lens development see Reza and Yasuda, 2004). Thus, the degenerating CF lens epithelium proliferates normally, and lens degeneration seems to be due exclusively to apoptosis of fiber cells.…”

Section: Proliferation and Apoptosis Patternsmentioning

confidence: 99%

“…The CMZ is capable of producing all retinal cell types and allows continuous growth of the retina throughout the life of these animals (for review see Perron and Harris, 2000). Proper eye formation also depends largely on specific and reciprocal interactions between the eye cup and the ectodermal thickening of the lens placode: the invagination of this placode forms an open pit, which finally closes in the lens vesicle and whose inner pole cells enlarges and forms the lens fibers (for review see Reza and Yasuda, 2004).…”

mentioning

confidence: 99%

Developmental mechanisms for retinal degeneration in the blind cavefish Astyanax mexicanus

Alunni¹,

Menuet²,

Candal³

et al. 2007

J of Comparative Neurology

100

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The sighted surface-dwelling (surface fish, SF) and the blind cave-living (cavefish, CF) forms of Astyanax mexicanus offer a unique opportunity to study the evolutionary changes in developmental mechanisms that lead to retinal degeneration. Previous data have shown the role of increased midline Sonic Hedgehog (Shh) signalling in cavefish eye degeneration (Yamamoto et al. [2004] Nature 431:844-847). Here, we have compared the major steps of eye development in SF and CF between 14 hours and 5 days of development. We have analyzed cell proliferation through PCNA and phospho-histone H3 staining and apoptosis through TUNEL and live LysoTracker analysis. We have assessed the expression of the major eye development signalling factors Shh and Fgf8, and the eye patterning genes Pax6, Lhx2, Lhx9, and Vax1, together with the differentiation marker GAD65. We show that eye development is retarded in CF and that cell proliferation in CF retina is proportionately similar to SF during early development, yet the retina degenerates after massive apoptosis in the lens and widespread cell death throughout the neuroretina. Moreover, and surprisingly, the signalling, patterning, and differentiation processes leading to the establishment of retinal layers and cell types happen almost normally in CF, although some signs of disorganization, slight heterochronies, and a lack of expression gradients are observable. Our data demonstrate that the evolutionary process of eye degeneration in the blind CF does not occur because of patterning defects of the retina and are consistent with the proposed scenario in which the trigger for eye degeneration in CF is lens apoptosis.

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“…This is an interesting and somewhat rare example of an environmental influence upon a developmental process. It would be worthwhile to compare presumptive lens tissues under the two different temperatures in terms of expression of developmental genes, particularly those regulating crystallin genes now identified (Kondoh, 1999;Kondoh et al, 2004;Reza and Yasuda, 2004).…”

Section: A Choice Of Developmental Mechanisms: Dependent or Independementioning

confidence: 99%

From embryonic induction to cell lineages: revisiting old problems for modern study

Okada¹

2004

Int. J. Dev. Biol.

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A history of embryological studies of lens development and regeneration is sketched, paying special attention to the contribution of these studies to the conceptual aspect of embryology and later developmental biology. Emphasis is made on the fact that the interaction of different tissues during development, namely embryonic induction, was first discovered during studies of the lens and that the degree of the dependence of lens development on the inductive effect of the eye-cup varies among different species. Studies along the line of comparativeexperimental embryology at the species level should be informative, in particular in combination with the recent trend of evo-devo studies. The processes of lens regeneration and in vitro transdifferentiation indicate the existence of multiple cell lineages with the potential of lens development in one animal. The occurrence of Wolffian lens regeneration in nature can be reconsidered from the new "eco-devo" viewpoint.

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Lens differentiation and crystallin regulation: a chick model

Cited by 35 publications

References 117 publications

The role of a lens survival pathway including sox2 and αA-crystallin in the evolution of cavefish eye degeneration

The role of a lens survival pathway including sox2 and αA-crystallin in the evolution of cavefish eye degeneration

Developmental mechanisms for retinal degeneration in the blind cavefish Astyanax mexicanus

From embryonic induction to cell lineages: revisiting old problems for modern study

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