Apoptosis in early ocular morphogenesis in the mouse

Laemle, Lois K.; Puszkarczuk, Michele; Feinberg, Richard N.

doi:10.1016/s0165-3806(98)00153-9

Cited by 45 publications

(44 citation statements)

References 15 publications

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“…The extensive apoptosis that occurs in the wild-type optic stalk (Fig. 3Q,S) (Laemle et al, 1999;Silver and Hughes, 1974) was reduced in the absence of Lhx2 (Fig. 3R,T), further indicating problems with dorsoventral patterning.…”

Section: Research Articlementioning

confidence: 97%

Lhx2links the intrinsic and extrinsic factors that control optic cup formation

et al. 2009

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A crucial step in eye organogenesis is the transition of the optic vesicle into the optic cup. Several transcription factors and extracellular signals mediate this transition, but whether a single factor links them into a common genetic network is unclear. Here, we provide evidence that the LIM homeobox gene Lhx2, which is expressed in the optic neuroepithelium, fulfils such a role. In Lhx2 -/-mouse embryos, eye field specification and optic vesicle morphogenesis occur, but development arrests prior to optic cup formation in both the optic neuroepithelium and lens ectoderm. This is accompanied by failure to maintain or initiate the expression patterns of optic-vesicle-patterning and lens-inducing determinants. Of the signaling pathways examined, only BMP signaling is noticeably altered and Bmp4 and Bmp7 mRNAs are undetectable. Lhx2 -/-optic vesicles and lens ectoderm upregulate Pax2, Fgf15 and Sox2 in response to BMP treatments, and Lhx2 genetic mosaics reveal that transcription factors, including Vsx2 and Mitf, require Lhx2 cell-autonomously for their expression. Our data indicate that Lhx2 is required for optic vesicle patterning and lens formation in part by regulating BMP signaling in an autocrine manner in the optic neuroepithelium and in a paracrine manner in the lens ectoderm. We propose a model in which Lhx2 is a central link in a genetic network that coordinates the multiple pathways leading to optic cup formation.

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Section: Research Articlementioning

confidence: 97%

Lhx2links the intrinsic and extrinsic factors that control optic cup formation

et al. 2009

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“…The neural tube defects of Apaf1-null mutant embryos are associated with both increased cell proliferation and reduced cell death (Cecconi et al, 1998;Yoshida et al, 1998). In addition, the link between apoptosis and optic fissure development has been previously described (Laemle et al, 1999;Ozeki et al, 2000;Trousse et al, 2001), although the precise role it plays in eye development should be further investigated. More recently, Bcl6 and Bcl6 interacting corepressor (Bcor) were found to act together in repressing p53-dependent apoptosis in the developing optic cup, such that disruption of their function prevents optic fissure closure .…”

Section: Introductionmentioning

confidence: 93%

Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling

et al. 2016

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The development of complex organs such as the eye requires a delicate and coordinated balance of cell division and cell death. Although apoptosis is prevalent in the proximoventral optic cup, the precise role it plays in eye development needs to be investigated further. In this study, we show that reduced apoptosis in the proximoventral optic cup prevents closure of the optic fissure. We also show that expression of ephrin A5 (Efna5) partially overlaps with Eph receptor B2 (Ephb2) expression in the proximoventral optic cup and that binding of EphB2 to ephrin A5 induces a sustained activation of JNK. This prolonged JNK signal promotes apoptosis and prevents cell proliferation. Thus, we propose that the unique cross-subclass interaction of EphB2 with ephrin A5 has evolved to function upstream of JNK signaling for the purpose of maintaining an adequate pool of progenitor cells to ensure proper closure of the optic fissure.

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“…Thus, we analyzed whether impairing RA synthesis, through the combined ablation of RALDH1 and RALDH3, alters the DV patterning of the retina. The identity of progenitor cells along the retina DV axis is specified by the expression of Tbx5, Vax2 and Pax2 genes (reviewed by McLaughlin et al, 2003), while the stereotyped distribution of apoptotic cells during retina development provides a reliable landmark of DV axis patterning (Laemle et al, 1999). The distribution patterns of Tbx5 and Vax2 transcripts at E10.5 (Fig.…”

Section: Ablation Of Rarb and Rarg In Neural Crest Cells Impairs Apopmentioning

confidence: 99%

Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells

et al. 2005

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(2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina. We additionally show that RALDH1 and RALDH3 are the only enzymes that are required for RA synthesis in the eye region from E10.5 to E13.5, and that patterning of the dorsoventral axis of the retina does not require RA. Research articleDevelopment 4790 role in DV patterning Dräger et al., 2001;Peters and Cepko, 2002;Sakai et al., 2004).RALDH2, whose genetic ablation kills embryos at E9.5 (Niederreither et al., 1999;Mic et al., 2002), is required between E8.5 and E9.5 for optic cup formation and for setting up the correct expression of RALDH3 at later stages in the forming eye (Mic et al., 2004). RALDH1-null mice are viable and do not exhibit ocular defects, even though they lack RAdependent activity in the dorsal retina and in the corresponding axonal projections at E16.5 (Fan et al., 2003). RALDH3-null mice, which die at birth from respiratory distress due to choanal atresia, display only discrete ocular malformations, namely a retrolenticular membrane and a mild shortening of the ventral retina (Dupé et al., 2003). Furthermore, neither RALDH1-null nor RALDH3-null mice exhibit an altered DV patterning of the retina (Fan et al., 2003; Dupé et al., 2003). These observations raised the question as to whether the loss of RALDH1 or RALDH3 could be functionally compensated by RALDH3 or RALDH1, respectively, or by other RALDH proteins expressed in the eye region. To gain further insight into the roles of RA signaling pathways in the developing eye, we have analyzed the ocular phenotype of mutant mice (1) lacking both RALDH1 and RALDH3, and (2) lacking RAR␤ and RAR␥ selectively in the NCC-derived periocular mesenchyme (POM). We demonstrate that RA produced in the neural retina, the retinal pigmented epithelium and the corneal ectoderm by RALDH1 and RALDH3 acts in a paracrine manner to selectively control the expression of several genes in POM cells, whereas it is dispensable for the DV patterning of the retina. Materials and methods MiceAll mice, with a mixed C57BL/6ϫ129/Sv (50:50) genetic background, were housed in an animal facility licensed by the French Ministry of Agriculture , and all animal experiments were supervised by N.B.G. , who is qualified for experimenting with mice, in compliance with the European legislation on care and use of laboratory animals. The breeding diet (D03) contained 25000 UI of vitamin A per kg (UAR, Villemoisson sur Orge, France) and was provided ad libitum. Heterozygous mice were mated overnight, and animals with a vaginal plug at noon of the next day were considered as embryonic day (E) 0.5. Mice bearing loxP-flanked (floxed) RAR␤ (Rarb +/L2) and RAR␥ (Rarg +/L2) genes (Chapellier et al., 2002a; Chapellier, 2002b), as well as the Rare-hsp68-lacZ (Rossant et al., 1991), R26R (Soriano, 1999) and Wnt1-Cre (Danielian et al., 1998) transgenic mice were genotyped as described. Note that mutant fetuses lacking both RALDH1 and RALDH3 (hereafter designa...

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Apoptosis in early ocular morphogenesis in the mouse

Cited by 45 publications

References 15 publications

Lhx2links the intrinsic and extrinsic factors that control optic cup formation

Lhx2links the intrinsic and extrinsic factors that control optic cup formation

Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling

Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells

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