Foxn4 Controls the Genesis of Amacrine and Horizontal Cells by Retinal Progenitors

Li, Shengguo; Mo, Zeqian; Yang, Xuejie; Price, Sandy M.; Shen, Michael M.; Xiang, Mengqing

doi:10.1016/j.neuron.2004.08.041

Cited by 225 publications

(298 citation statements)

References 56 publications

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“…6I-O) (data not shown). Consistent with the loss of Foxn4 expression, the expression of its downstream targets, Math3 and NeuroD1 (Li et al, 2004), was also undetectable in the Sufu-null region (Fig. 6O) (data not shown).…”

Section: Sufu Is Required To Maintain Rpc Multipotencysupporting

confidence: 62%

“…jneurosci.org as supplemental material), indicating that GC differentiation in this region was abrogated, rather than delayed. Similarly, the expression of Foxn4 and Crx, which are required for amacrine/ horizontal cell (Li et al, 2004) and rod/cone photoreceptor development (Furukawa et al, 1999), respectively, was also undetectable in the Sufu-null region of the ventral retina at E12.5 and E14.5 (Fig. 6I-O) (data not shown).…”

Section: Sufu Is Required To Maintain Rpc Multipotencymentioning

confidence: 78%

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Suppressor of Fused Is Required to Maintain the Multipotency of Neural Progenitor Cells in the Retina

Cwinn¹,

Mazerolle²,

McNeill³

et al. 2011

J. Neurosci.

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The morphogen sonic hedgehog (Shh) plays a crucial role in development of the CNS, including the neural retina. Suppressor of fused (Sufu) has been recently identified as a critical regulator of Hh signaling in mammals. However, the precise roles that Sufu plays in the regulation of proliferation and cell-fate decisions in neural progenitors is unknown. Here, we have addressed these questions by conditionally deleting Sufu in mouse multipotent retinal progenitor cells (RPCs). Sufu deletion in RPCs results in transient increases in Hh activity and proliferation followed by developmentally premature cell-cycle exit. Importantly, we demonstrate a novel role for Sufu in the maintenance of multipotency in RPCs. Sufu-null RPCs downregulate transcription factors required to specify or maintain RPC identity (Rax, Vsx2) and multipotency (Pax6) but continue to express the neural progenitor marker Sox2. These cells fail to express retinal lineage-specific transcription factors, such as Math5, and adopt an amacrine or horizontal cell fate at the expense of all other classes of retinal neurons. Genetic elimination of Gli2 in Sufu-null RPCs attenuates Hh pathway activity and restores multipotency in neural progenitors. These data provide novel evidence that Sufu-mediated antagonism of Hh/Gli2 signaling is required to maintain RPC multipotency and identity.

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Section: Sufu Is Required To Maintain Rpc Multipotencysupporting

confidence: 62%

Section: Sufu Is Required To Maintain Rpc Multipotencymentioning

confidence: 78%

Suppressor of Fused Is Required to Maintain the Multipotency of Neural Progenitor Cells in the Retina

Cwinn¹,

Mazerolle²,

McNeill³

et al. 2011

J. Neurosci.

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“…Nevertheless, deletion of both Oc1 and Oc2 together leads to complete failure of HC genesis, confirming the redundancy of these two factors in the HC lineage. Two major regulators involved in the HC fate are FoxN4 and Ptf1a, with FoxN4 being upstream (29,30). We recently showed that Oc1 functions together with Ptf1a at the same level in the regulatory hierarchy to promote the HC fate and inhibit the amacrine cell fate (14).…”

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.

125

134

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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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“…Staining was performed for a few hours to overnight at 30°C or 37°C in PBS containing 0.02% Nonidet P-40, 0.01% sodium deoxycholate, 5 mM potassium ferricyanide, 5 mM potassium ferrocyanide, and 0.5 mg/ml X-gal. TUNEL labeling and immunostaining using rabbit anti-calbindin D28K (1:800, Swant) and mouse anti-Brn3a (1:50, Chemicon) antibodies were performed also as previously described (Li et al, 2004a).…”

Section: X-gal Staining Tunel Labeling and Immunohistochemistrymentioning

confidence: 99%

Barhl1 is required for maintenance of a large population of neurons in the zonal layer of the superior colliculus

Xiang

2006

Developmental Dynamics

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The mammalian superior colliculus of the midbrain is a brainstem center that integrates sensorimotor signals involved in the control of orienting behaviors. Its structure is characterized by seven well-organized cellular and fibrous layers associated with distinct physiological properties. To date, however, little is known about the molecular bases governing the lamination, differentiation, and survival of superior collicular neurons. Barhl1 is a homeodomain transcription factor that has been demonstrated to play an essential role in maintaining inner ear hair cells, cerebellar granule cells, and precerebellar neurons. We show here that Barhl1 exhibits a select expression pattern in the superior colliculus with positive neurons largely restricted to the zonal layer, as visualized by the ␤-galactosidase activity expressed from the lacZ reporter knocked in the Barhl1 locus. Targeted disruption of Barhl1 results in the loss of a large population of neurons from the zonal layer of the superior colliculus, as indicated by reduced ␤-galactosidase staining and marker gene expression as well as by increased apoptotic cell death. Taken together, these data suggest that Barhl1 is crucially required for the survival but not for the specification of zonal layer neurons in the superior colliculus. Developmental Dynamics 235:2260 -2265, 2006.

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Foxn4 Controls the Genesis of Amacrine and Horizontal Cells by Retinal Progenitors

Cited by 225 publications

References 56 publications

Suppressor of Fused Is Required to Maintain the Multipotency of Neural Progenitor Cells in the Retina

Suppressor of Fused Is Required to Maintain the Multipotency of Neural Progenitor Cells in the Retina

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Barhl1 is required for maintenance of a large population of neurons in the zonal layer of the superior colliculus

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