Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells

Jiang, Ying; Ding, Qian; Xie, Xiaoling; Libby, Richard T.; Lefebvre, Véronique; Gan, Lin

doi:10.1074/jbc.m113.478503

Cited by 123 publications

(118 citation statements)

References 43 publications

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“…To verify that these phenotypes were due to loss of Tbr2 in the retina, we stained P1 brains for Tbr2 in retinal targets and found no Tbr2 ϩ cells in the OPN, IGL, LGN, or PPN; however, consistent with previous reports (Bulfone et al, 1999;Kimura et al, 1999), labeled cells were found in the hippocampus (data not shown).…”

Section: Tbr2 Is Required For the Formation Of Retinal Projections Tosupporting

confidence: 61%

“…Therefore, differentiation from progenitor cells is significantly influenced by the regulated expression of transcription factors (Shirasaki and Pfaff, 2002). Numerous transcription factors, many of which control cell fate in the nervous system and elsewhere, are expressed in RGCs (Brown et al, 2001;Mu and Klein, 2004;Badea et al, 2009;Jiang et al, 2013), although none have been linked directly to specific RGC functional types and accompanying neural circuits. Here, we show that Tbr2 (also known as Eomesodermin), a T-box transcription factor that plays a critical role in the development of neural and non-neural tissues (Russ et al, 2000;Arnold et al, 2008;Mao et al, 2008;Sessa et al, 2008), is essential for the specification of RGC types that participate in non-imageforming visual circuits.…”

Section: Introductionmentioning

confidence: 99%

“…There are thousands of neuronal types in the CNS with different morphologies, intrinsic properties, and connection patterns (Nelson et al, 2006;Luo et al, 2008;Masland, 2012). Derived from a common progenitor pool, each neuronal type uses a combination of transcriptional regulation and environmental cues to express a set of genes critical for inclusion into specific circuits.…”

Section: Introductionmentioning

confidence: 99%

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Tbr2 Is Required to Generate a Neural Circuit Mediating the Pupillary Light Reflex

2014

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There are ϳ20 types of retinal ganglion cells (RGCs) in mice, each of which has distinct molecular, morphological, and physiological characteristics. Each RGC type sends axon projections to specific brain areas that execute light-dependent behaviors. Here, we show that the T-box transcription factor Tbr2 is required for the development of several RGC types that participate in non-image-forming circuits. These types are molecularly distinct, project to non-image-forming targets, and include intrinsically photosensitive RGCs. Tbr2 mutant mice have reduced retinal projections to non-image-forming nuclei and an attenuated pupillary light reflex. These data demonstrate that Tbr2 acts to execute RGC type choice and/or survival in a set of RGCs that mediates light-induced subconscious behaviors.

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Section: Tbr2 Is Required For the Formation Of Retinal Projections Tosupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tbr2 Is Required to Generate a Neural Circuit Mediating the Pupillary Light Reflex

2014

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“…Key regulators for RGC development include Atoh7 (also known as Math5), Pou4f2, and Isl1, with Atoh7 functioning upstream, and Pou4f2 and Isl1 downstream (32). Sox4 and Sox11 also seem to be involved in the early stages of RGC genesis, downstream of Atoh7 but independent of Pou4f2 (33). Oc1 and Oc2 are both expressed in RPCs and postmitotic RGCs, and thus appear to function at two levels: one during RGC genesis (at the same level as Atoh7) and the other after RGC genesis (downstream of Atoh7) to regulate RGC subtype specification (15).…”

Section: Potential Mechanisms By Which Oc1 and Oc2 Function In Multiplementioning

confidence: 99%

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Sapkota

Chintala

et al. 2014

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

130

136

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Previously, we have shown that Onecut1 (Oc1) and Onecut2 (Oc2) are expressed in retinal progenitor cells, developing retinal ganglion cells (RGCs), and horizontal cells (HCs). However, in Oc1-null mice, we only observed an 80% reduction in HCs, but no defects in other cell types. We postulated that the lack of defects in other cell types in Oc1-null retinas was a result of redundancy with Oc2. To test this theory, we have generated Oc2-null mice and now show that their retinas also only have defects in HCs, with a 50% reduction in their numbers. However, when both Oc1 and Oc2 are knocked out, the retinas exhibit more profound defects in the development of all early retinal cell types, including completely failed genesis of HCs, compromised generation of cones, reduced production (by 30%) of RGCs, and absence of starburst amacrine cells. Cone subtype diversification and RGC subtype composition also were affected in the double-null retina. Using RNA-Seq expression profiling, we have identified downstream genes of Oc1 and Oc2, which not only confirms the redundancy between the two factors and renders a molecular explanation for the defects in the double-null retinas, but also shows that the onecut factors suppress the production of the late cell type, rods, indicating that the two factors contribute to the competence of retinal progenitor cells for the early retinal cell fates. Our results provide insight into how onecut factors regulate the creation of cellular diversity in the retina and, by extension, in the central nervous system in general.transcription factors | neural development | retinal development | cell fate determination | gene regulation

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“…Animals-Generation of the Sox11 fx/fx mice has been described previously (28). Mouse strains for Wnt1-Cre, Dermo1-Cre, Osr2-IRESCre, K14-Cre, Foxg1-Cre, Nestin-Cre, and EIIaCre were purchased from The Jackson Laboratory.…”

Section: Methodsmentioning

confidence: 99%

Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence

Huang

Xiao

Bao

et al. 2016

Journal of Biological Chemistry

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Mouse gene inactivation has shown that the transcription factor Sox11 is required for mouse palatogenesis. However, whether Sox11 is primarily involved in the regulation of palatogenesis still remains elusive. In this study, we explored the role of Sox11 in palatogenesis by analyzing the developmental mechanism in cleft palate formation in mutants deficient in Sox11. Sox11 is expressed both in the developing palatal shelf and in the surrounding structures, including the mandible. We found that cleft palate occurs only in the mutant in which Sox11 is directly deleted. As in the wild type, the palatal shelves in the Sox11 mutant undergo outgrowth in a downward direction and exhibit potential for fusion and elevation. However, mutant palatal shelves encounter clefting, which is associated with a malpositioned tongue that results in physical obstruction of palatal shelf elevation at embryonic day 14.5 (E14.5). We found that loss of Sox11 led to reduced cell proliferation in the developing mandibular mesenchyme via Cyclin D1, leading to mandibular hypoplasia, which blocks tongue descent. Extensive analyses of gene expression in Sox11 deficiency identified FGF9 as a potential candidate target of Sox11 in the modulation of cell proliferation both in the mandible and the palatal shelf between E12.5 and E13.5. Finally we show, using in vitro assays, that Sox11 directly regulates the expression of Fgf9 and that application of FGF9 protein to Sox11-deficient palatal shelves restores the rate of BrdU incorporation. Taken together, the palate defects presented in the Sox11 loss mutant mimic the clefting in the Pierre Robin sequence in humans.

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Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells

Cited by 123 publications

References 43 publications

Tbr2 Is Required to Generate a Neural Circuit Mediating the Pupillary Light Reflex

Tbr2 Is Required to Generate a Neural Circuit Mediating the Pupillary Light Reflex

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence

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