The Role of NeuroD as a Differentiation Factor in the Mammalian Retina

Ahmad, Iqbal; Acharya, Harsha R.; Rogers, Jim; Shibata, Annemarie; Smithgall, Thomas E.; Dooley, Constance M.

doi:10.1385/jmn:11:2:165

Cited by 46 publications

(34 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although previous studies of NeuroD1 in the retina have shown that the gene is expressed in developing and mature photoreceptors (Kanekar et al, 1997;Ahmad et al, 1998;Wang, 1998, 2004;Morrow et al, 1999), double-labeling for NeuroD1 expression and BrdU shows that the majority of the NeuroD1-expressing cells are postmitotic. This is consistent with our previous findings that TR␤2 and its heterodimeric partner, RXR␥, are also expressed in newly postmitotic cone photoreceptors (Ng et al, 2001;Roberts et al, 2005Roberts et al, , 2006Jones et al, 2007).…”

Section: Discussionmentioning

confidence: 94%

“…NeuroD1 is expressed in the developing and mature retina in both photoreceptors and amacrine cells in frog, chick, and mammals (Kanekar et al, 1997;Ahmad et al, 1998;Yan and Wang, 1998;Morrow et al, 1999;Pennesi et al, 2003). In other regions of the CNS, although primarily expressed in postmitotic cells, NeuroD1 has also been found in some mitotically active progenitor cells (Lee et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

“…Several transcription factors are known to be expressed in developing cones before the onset of TR␤2, including Otx2 (Nishida et al, 2003), Crx (Furukawa et al, 1997), and Rb (Zhang et al, 2004). In addition, several members of the basic helix-loop-helix (bHLH) class of transcription factors are expressed in developing photoreceptors, including Math3 and NeuroD1 (Ahmad et al, 1998;Yan and Wang, 1998Morrow et al, 1999;Pennesi et al, 2003). Recent analysis of the Thrb gene that encodes TR␤2 (Jones et al, 2007) identified a cone-specific, intronic control region.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NeuroD1 Regulates Expression of Thyroid Hormone Receptor β2 and Cone Opsins in the Developing Mouse Retina

et al. 2008

View full text Add to dashboard Cite

The correct patterning of opsin expression in cone photoreceptors is critical for normal color vision. Thyroid hormone, and one of its receptors [thyroid hormone receptor ␤2 (TR␤2)], is an important regulator of opsin expression during cone photoreceptor development. Mice have two genes, encoding medium-wavelength (M) and short-wavelength (S) cone opsins. Targeted deletion of TR␤2 leads to a uniform expression of S-opsin in all cone photoreceptors and a loss of M-opsin. The control of expression of TR␤2 is therefore central to cone differentiation, yet there is little known about its regulation in the retina. We now report that the proneural bHLH (basic helix-loophelix) transcription factor, NeuroD1, is necessary for sustained expression of TR␤2 in immature cone photoreceptors. Mice deficient in NeuroD1 develop an opsin phenotype virtually identical with that of TR␤2-deficient mice: all cones express S-opsin, and none expresses M-opsin. The introduction of NeuroD1 into embryonic retinal explants from NeuroD1 Ϫ/Ϫ mice restores TR␤2 expression. NeuroD1 binds an E-box in the intron control region of the TR␤2 gene that mediates cone-specific expression, suggesting that NeuroD1 is a critical contributory factor to the expression of TR␤2 in cones. These results thus connect the proneural pathway with opsin selection to ensure correct cone patterning during retinal development.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NeuroD1 Regulates Expression of Thyroid Hormone Receptor β2 and Cone Opsins in the Developing Mouse Retina

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Electrophysiological recordings allowed a single-cell analysis in the densely packed hilar region, and we obtained direct evidence for the presence of normal interneurons but a virtual lack of differentiated GC. Because both cell types are derived from one pool of early progenitors, it is possible that neuronal bHLH proteins participate also in a late step of lineage decision (Ahmad et al, 1998;Yan and Wang, 1998;Morrow et al, 1999). However, the abundance of immature cells that express some (but not all) neuronal differentiation markers demonstrates that one essential function of NEX, BETA2/NeuroD, and presumably also NDRF, is the control of terminal neuronal differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…This suggested a role in differentiation, whereas initial gain-of-function experiments (involving overexpression in frog oocytes) demonstrated, by neurogenic conversion, that at least BETA2/NeuroD and NDRF/NeuroD2 can act as determination factors (Lee et al, 1995;McCormick et al, 1996). Given the uncertainty of abnormal timing in these and related experiments involving ectopic expression (Ahmad et al, 1998;Yan and Wang, 1998;Morrow et al, 1999), the normal function of neuronal bHLH proteins has remained unclear. Moreover, initial gene targeting experiments have revealed that BETA2/NeuroD is essential for pancreas development, and its loss of function is lethal, presumably because of early postnatal diabetic failure (Naya et al, 1997).…”

Section: Abstract: Dentate Gyrus; Granule Cells; Neuronal Differentimentioning

confidence: 99%

Neuronal Basic Helix-Loop-Helix Proteins (NEX and BETA2/Neuro D) Regulate Terminal Granule Cell Differentiation in the Hippocampus

et al. 2000

View full text Add to dashboard Cite

The transcription factors neuronal helix-loop-helix protein (NEX)/mammalian atonal homolog 2 (Math-2), BETA2/neuronal determination factor (NeuroD), and NeuroD-related factor (NDRF)/NeuroD2 comprise a family of Drosophila atonalrelated basic helix-loop-helix (bHLH) proteins with highly overlapping expression in the developing forebrain. The ability of BETA2/NeuroD and NDRF to convert ectodermal cells into neurons after mRNA injection into Xenopus oocytes suggested a role in specifying neuronal cell fate. However, neuronal bHLH genes are largely transcribed in CNS neurons, which are fully committed. Here we analyze a defect in mice lacking BETA2/ NeuroD, and in NEX*BETA2/NeuroD double mutants, demonstrating that bHLH proteins are required in vivo for terminal neuronal differentiation. Most strikingly, presumptive granule cells of the dentate gyrus are generated but fail to mature, lack normal sodium currents, and show little dendritic arborization. Long-term hippocampal slice cultures demonstrate secondary alterations of entorhinal and commissural/associational projections. The primary developmental arrest appears to be restricted to granule cells in which an autoregulatory system involving all three neuronal bHLH genes has failed.

show abstract

Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system

et al. 2000

View full text Add to dashboard Cite

NeuroD/BETA2, a basic helixloop-helix transcription factor, has been shown to play a role in tissue-specific differentiation of pancreatic and enteroendocrine cells. To gain further insight into the function of neuroD/ BETA2 in the nervous system development, we examined the expression pattern of neuroD/ BETA2 during embryonic and postnatal development by using in situ hybridization. Dynamic changes of neuroD/BETA2 expression in the central nervous system were observed during embryogenesis, especially in telencephalon, hippocampus, cerebellum, spinal cord, and olfactory epithelium. Moderate level of expression was also detected in developing pancreas in early embryogenesis. Although the neuroD/BETA2 expression in cerebellum and hippocampus increased over time, expression in cerebral cortex, spinal cord, as well as in fetal pancreas gradually decreased as embryogenesis proceeded. High level of the neuroD/BETA2 expression in developing cerebellum and hippocampus persisted throughout postnatal development and remained at a stable level in the adult brain. Interestingly, neuroD/BETA2 expression was detected not only in postmitotic but also in mitotic cells, as was evident in its expression in external granular layer of cerebellum and granule cells of the dentate gyrus during postnatal development. This observation suggests that neuroD/BETA2 may have a unique role in proliferation, differentiation, or both, of granule cells of cerebellum and dentate gyrus.

show abstract

The Role of NeuroD as a Differentiation Factor in the Mammalian Retina

Cited by 46 publications

References 56 publications

NeuroD1 Regulates Expression of Thyroid Hormone Receptor β2 and Cone Opsins in the Developing Mouse Retina

NeuroD1 Regulates Expression of Thyroid Hormone Receptor β2 and Cone Opsins in the Developing Mouse Retina

Neuronal Basic Helix-Loop-Helix Proteins (NEX and BETA2/Neuro D) Regulate Terminal Granule Cell Differentiation in the Hippocampus

Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system

Contact Info

Product

Resources

About