Control of lens development by Lhx2-regulated neuroretinal FGFs

Thein, Thuzar; Melo, Jimmy de; Zibetti, Cristina; Clark, Brian S.; Juarez, Felicia; Blackshaw, Seth

doi:10.1242/dev.137760

Cited by 20 publications

(12 citation statements)

References 53 publications

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“…It appears that expression of BMPs in the dorsal optic vesicle is stabilized by Wnt signals from the ectoderm via β-catenin-independent and GSK3β-dependent pathway [137]. The Lhx2-BMP axis described above was further elaborated through a “delayed” inactivation of Lhx2 in the optic cup from E10.5 that disrupted both lens and retinal morphogenesis and reduced the expression of Fgf3, Fgf9, Fgf15, Etv5/ERM, Etv1/ER81, and Bmp4 in the mutated optic cup [138]. Importantly, this study identifies a complement of FGFs acting in vivo during lens fiber cell differentiation.…”

Section: Lens Morphogenesis and Gene Regulatory Networkmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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Ocular lens development represents an advantageous system to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and underlying gene regulatory networks. Spatiotemporaly regulated domains of BMP, FGF, and other signaling molecules in the late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate expression of the lens structural proteins, the crystallins. A multitude of cross-talks between a diverse array of signaling pathways control the complexity and order of the lens morphogenetic processes and its transparency.

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Section: Lens Morphogenesis and Gene Regulatory Networkmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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“…Germline deletion of Lhx2 results in complete anophthalmia (Porter et al, 1997). However, conditional neuroretinal knockout of Lhx2 (Lhx2ΔcKO) during later retinogenic timepoints results in premature cell cycle exit, altered RPC competence, loss of neuroretinal-derived FGFs (which results in a secondary arrest in lens fiber development) and disrupted MG development (Gordon et al, 2013;de Melo et al, 2016a;Gueta et al, 2016;Thein et al, 2016). The differentiation of neurons generated following Lhx2ΔcKO-induced cell cycle exit appears grossly normal, although neuronal diversity is limited by RPC competence at the stage when mitotic exit occurs (Gordon et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina

et al. 2018

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Precise control of the relative ratio of retinal neurons and glia generated during development is essential for visual function. We show that , which encodes a LIM-homeodomain transcription factor essential for specification and differentiation of retinal Müller glia, also plays a crucial role in the development of retinal neurons. Overexpression of with its transcriptional co-activator triggers cell cycle exit and inhibits both Notch signaling and retinal gliogenesis./ overexpression also induces the formation of wide-field amacrine cells (wfACs). In contrast, , which encodes a negative regulator of LDB1, is necessary for the initiation of retinal gliogenesis. We also show that Lhx2-dependent neurogenesis and wfAC formation requires and , and that Lhx2 is necessary for their expression, although overexpression of/ does not elevate expression of these proneural bHLH factors. Finally, we demonstrate that the relative level of the LHX2-LDB1 complex in the retina decreases in tandem with the onset of gliogenesis. These findings show that control of function by and underpins the coordinated differentiation of neurons and Müller glia in postnatal retina.

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“…Lhx2 cKO embryos do not exhibit the OD/CMZ expansion phenotype but, rather, the up-regulation of a set of genes that are normally expressed in the thalamic eminence and anterodorsal hypothalamus (51). Chx10-Cre;Lhx2 f/f mice show an early arrest in lens fiber development due to the down-regulation of Fgfs in the retina (72). In contrast, the lens is smaller but no defects in lens fiber differentiation are evident in Meis1/2 cKO mice (Fig.…”

Section: Discussionmentioning

confidence: 92%

Meis homeobox genes control progenitor competence in the retina

Dupacova

Antosova

Pačes

et al. 2021

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

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The vertebrate eye is derived from the neuroepithelium, surface ectoderm, and extracellular mesenchyme. The neuroepithelium forms an optic cup in which the spatial separation of three domains is established, namely, the region of multipotent retinal progenitor cells (RPCs), the ciliary margin zone (CMZ)—which possesses both a neurogenic and nonneurogenic potential—and the optic disk (OD), the interface between the optic stalk and the neuroretina. Here, we show by genetic ablation in the developing optic cup that Meis1 and Meis2 homeobox genes function redundantly to maintain the retinal progenitor pool while they simultaneously suppress the expression of genes characteristic of CMZ and OD fates. Furthermore, we demonstrate that Meis transcription factors bind regulatory regions of RPC-, CMZ-, and OD-specific genes, thus providing a mechanistic insight into the Meis-dependent gene regulatory network. Our work uncovers the essential role of Meis1 and Meis2 as regulators of cell fate competence, which organize spatial territories in the vertebrate eye.

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Control of lens development by Lhx2-regulated neuroretinal FGFs

Cited by 20 publications

References 53 publications

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina

Meis homeobox genes control progenitor competence in the retina

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