Relationship between delta‐like and proneural bHLH genes during chick retinal development

Nelson, Branden R.; Reh, Thomas A.

doi:10.1002/dvdy.21550

Cited by 42 publications

(48 citation statements)

References 93 publications

(154 reference statements)

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“…According to a previous model, Delta-like genes should be expressed in the differentiating neurons (Henrique et al, 1997). Surprisingly, we found that Dll1 was expressed in progenitor cells, and while Dll4 was also expressed in some progenitors, the cohort of differentiating newborn neurons primarily expressed Dll4 (Nelson and Reh, 2008). These results suggested that progenitor cells are themselves a primary source of Notch ligands and may mutually inhibit their own differentiation through activation of Notch receptors expressed in neighboring progenitors.…”

Section: Introductionmentioning

confidence: 47%

“…Dll1, Dll4, Ascl1, and Neurog2 are all expressed in progenitors and exhibit similar expression kinetics during neuronal differentiation (Nelson and Reh, 2008). Moreover, we reported that overexpression of Ascl1 led to an increase in both Dll1 and Dll4 gene expression and Notch signaling activity (Nelson and Reh, 2008).…”

Section: Introductionmentioning

confidence: 81%

“…When we investigated the relationship between Delta-like and proneural bHLH genes during chick retinal development, we found that of all of the proneural bHLH genes, both Ascl1 and Neurog2 were expressed in progenitors that may also express Delta-like genes; however, only Ascl1 was found to upregulate Delta-like gene expression and Notch signaling activity in a gain-of-function assay (Nelson and Reh, 2008). To determine whether Ascl1 or Neurog2 are required for Delta-like gene expression, we used QPCR to measure the level of expression of Notch pathway components in the retinas from Ascl1 and Neurog2 mutant mice.…”

Section: Ascl1 Regulates Delta-like Gene Expression and Notch Signalimentioning

confidence: 99%

“…Multiple Notch ligands are present during vertebrate retinal development, complicating this simple lateral inhibitory model (Lindsell et al, 1996;Bao and Cepko, 1997;Valsecchi et al, 1997;Henrique et al, 1997;Wang et al, 1998;Benedito and Duarte, 2005;Nimmagadda et al, 2007;Nelson et al, 2007a;Nelson and Reh, 2008). Vertebrates have two orthologous families of canonical Notch ligands, Delta-like and Jagged, but have different numbers of paralogs within each family depending on the species.…”

Section: Introductionmentioning

confidence: 99%

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Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

Nelson

Hartman

Ray

et al. 2009

Developmental Dynamics

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SummaryDelta gene expression in Drosophila is regulated by proneural bHLH transcription factors, such as acheate-scute. In vertebrates, multiple Delta-like and proneural bHLH genes are expressed during neurogenesis, especially in the retina. We recently uncovered a relationship between Acheatescute like 1 (Ascl1), Delta-like genes, and Notch in chick retinal progenitors. Here, we report that mammalian retinal progenitors are also the primary source of Delta-like genes, likely signaling through Notch among themselves, while differentiating neurons expressed Jagged2. Ascl1 is coexpressed in Delta-like and Notch active progenitors, and required for normal Delta-like gene expression and Notch signaling. We also reveal a role for Ascl1 in the regulation of Hes6, a proneurogenic factor that inhibits Notch signaling to promote neural rather than glial differentiation. Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1 deficient retina.

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Section: Introductionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 81%

Section: Ascl1 Regulates Delta-like Gene Expression and Notch Signalimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

Nelson

Hartman

Ray

et al. 2009

Developmental Dynamics

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“…The Cath6-positive region was also complementary to the regions expressing Notch1, Cash1, and Cath5 (Fig. 2F,G), which are the markers for progenitor cells, preneurogenic progenitor cells, and nascent neurons before terminal differentiation, respectively (Henrique et al, 1997;Matter-Sadzinski et al, 2001;Nelson and Reh, 2008). These data suggest that Cath6 is specifically expressed in stem cell-like progenitor cells but not in the iris/ciliary epithelium or in differentiating progenitor cells.…”

Section: Cath6 Is Expressed In the Retinal Stem-like Progenitor Cellsmentioning

confidence: 79%

Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retina

Kubo

Nakagawa

2010

Developmental Dynamics

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Basic helix-loop-helix (bHLH) transcription factors play important roles in cell type specification and differentiation during the development of the nervous system. In this study, we identified a chicken homolog of Atonal 8/ath6 (Cath6) and examined its role in the developing retina. Unlike other Atonal-family proneural genes that induce neuronal differentiation, Cath6 was expressed in stem cell-like progenitor cells in the marginal region of the retina, and its overexpression inhibited neuronal differentiation. A Cath6 fused with a VP16 transactivation domain recapitulated the inhibitory effect of Cath6 on neuronal differentiation, indicating that Cath6 functions as a transcription activator. These results demonstrate that Cath6 constitutes a unique member of the Atonal-family of genes in that it acts as a negative regulator of neuronal differentiation. Developmental Dynamics 239:2492-2500,

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Prognostic markers in triple‐negative breast cancer

Rakha

El-Sayed

Green

et al. 2006

Cancer

1,128

115

843

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Basic helix–loop–helix (bHLH) transcription factors play important roles in cell type specification and differentiation during the development of the nervous system. In this study, we identified a chicken homolog of Atonal 8/ath6 (Cath6) and examined its role in the developing retina. Unlike other Atonal‐family proneural genes that induce neuronal differentiation, Cath6 was expressed in stem cell‐like progenitor cells in the marginal region of the retina, and its overexpression inhibited neuronal differentiation. A Cath6 fused with a VP16 transactivation domain recapitulated the inhibitory effect of Cath6 on neuronal differentiation, indicating that Cath6 functions as a transcription activator. These results demonstrate that Cath6 constitutes a unique member of the Atonal‐family of genes in that it acts as a negative regulator of neuronal differentiation. Developmental Dynamics 239:2492–2500, 2010. © 2010 Wiley‐Liss, Inc.

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Relationship between delta‐like and proneural bHLH genes during chick retinal development

Cited by 42 publications

References 93 publications

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retina

Prognostic markers in triple‐negative breast cancer

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