Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

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Regulation of hippocampal neuronal differentiation by the basic helix-loop-helix transcription factors HES-1 and MASH-1

Journal of Neuroscience Research ◽

10.1002/(sici)1097-4547(19990501)56:3<229::aid-jnr2>3.0.co;2-z ◽

1999 ◽

Vol 56 (3) ◽

pp. 229-240 ◽

Cited By ~ 36

Author(s):

Paul Castella ◽

John A. Wagner ◽

Michael Caudy

Keyword(s):

Transcription Factors ◽

Neuronal Differentiation ◽

Basic Helix Loop Helix ◽

Helix Loop Helix

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Mediation of NGF signaling by post-translational inhibition of HES-1, a basic helix-loop-helix repressor of neuronal differentiation

Genes & Development ◽

10.1101/gad.11.23.3168 ◽

1997 ◽

Vol 11 (23) ◽

pp. 3168-3181 ◽

Cited By ~ 61

Author(s):

A. Strom ◽

P. Castella ◽

J. Rockwood ◽

J. Wagner ◽

M. Caudy

Keyword(s):

Neuronal Differentiation ◽

Basic Helix Loop Helix ◽

Helix Loop Helix ◽

Translational Inhibition ◽

Ngf Signaling

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Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells

Development ◽

10.1242/dev.114.1.75 ◽

1992 ◽

Vol 114 (1) ◽

pp. 75-87 ◽

Cited By ~ 9

Author(s):

J.E. Johnson ◽

K. Zimmerman ◽

T. Saito ◽

D.J. Anderson

Keyword(s):

Retinoic Acid ◽

Neuronal Differentiation ◽

Embryonal Carcinoma ◽

Model System ◽

Neuronal Morphology ◽

Carcinoma Cells ◽

P19 Cells ◽

Embryonal Carcinoma Cells ◽

Bhlh Genes ◽

P19 Embryonal Carcinoma Cells

MASH1 and MASH2, mammalian homologues of the Drosophila neural determination genes achaete-scute, are members of the basic helix-loop-helix (bHLH) family of transcription factors. We show here that murine P19 embryonal carcinoma cells can be used as a model system to study the regulation and function of these genes. MASH1 and MASH2 display complementary patterns of expression during the retinoic-acid-induced neuronal differentiation of P19 cells. MASH1 mRNA is undetectable in undifferentiated P19 cells but is induced to high levels by retinoic acid coincident with neuronal differentiation. In contrast, MASH2 mRNA is expressed in undifferentiated P19 cells and is repressed by retinoic acid treatment. These complementary expression patterns suggest distinct functions for MASH1 and MASH2 in development, despite their sequence homology. In retinoic-acid-treated P19 cells, MASH1 protein expression precedes and then overlaps expression of neuronal markers. However, MASH1 is expressed by a smaller proportion of cells than expresses such markers. MASH1 immunoreactivity is not detected in differentiated cells displaying a neuronal morphology, suggesting that its expression is transient. These features of MASH1 expression are similar to those observed in vivo, and suggest that P19 cells represent a good model system in which to study the regulation of this gene. Forced expression of MASH1 was achieved in undifferentiated P19 cells by transfection of a cDNA expression construct. The transfected cells expressing exogenous MASH1 protein contained E-box-binding activity that could be super-shifted by an anti-MASH1 antibody, but exhibited no detectable phenotypic changes. Thus, unlike myogenic bHLH genes, such as MyoD, which are sufficient to induce muscle differentiation, expression of MASH1 appears insufficient to promote neurogenesis.

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Deletion of the Prdm3 Gene Causes a Neuronal Differentiation Deficiency in P19 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21197192 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7192

Author(s):

Paweł Leszczyński ◽

Magdalena Śmiech ◽

Aamir Salam Teeli ◽

Effi Haque ◽

Robert Viger ◽

...

Keyword(s):

Retinoic Acid ◽

Mrna Expression ◽

Neuronal Differentiation ◽

Regulatory Mechanism ◽

Gene Knockout ◽

Luciferase Reporter ◽

P19 Cells ◽

Binding Factor ◽

Domain I

PRDM (PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain-containing) transcription factors are a group of proteins that have a significant impact on organ development. In our study, we assessed the role of Prdm3 in neurogenesis and the mechanisms regulating its expression. We found that Prdm3 mRNA expression was induced during neurogenesis and that Prdm3 gene knockout caused premature neuronal differentiation of the P19 cells and enhanced the growth of non-neuronal cells. Interestingly, we found that Gata6 expression was also significantly upregulated during neurogenesis. We further studied the regulatory mechanism of Prdm3 expression. To determine the role of GATA6 in the regulation of Prdm3 mRNA expression, we used a luciferase-based reporter assay and found that Gata6 overexpression significantly increased the activity of the Prdm3 promoter. Finally, the combination of retinoic acid receptors α and β, along with Gata6 overexpression, further increased the activity of the luciferase reporter. Taken together, our results suggest that in the P19 cells, PRDM3 contributed to neurogenesis and its expression was stimulated by the synergism between GATA6 and the retinoic acid signaling pathway.

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An adipogenic basic helix-loop-helix-leucine zipper type transcription factor (ADD1) mRNA is expressed and regulated by retinoic acid in osteoblastic cells

Molecular Endocrinology ◽

10.1210/me.10.10.1238 ◽

1996 ◽

Vol 10 (10) ◽

pp. 1238-1248 ◽

Cited By ~ 3

Author(s):

Y. Sawada

Keyword(s):

Transcription Factor ◽

Retinoic Acid ◽

Leucine Zipper ◽

Osteoblastic Cells ◽

Basic Helix Loop Helix ◽

Helix Loop Helix

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The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation

Development ◽

10.1242/dev.127.13.2933 ◽

2000 ◽

Vol 127 (13) ◽

pp. 2933-2943 ◽

Cited By ~ 7

Author(s):

S. Bae ◽

Y. Bessho ◽

M. Hojo ◽

R. Kageyama

Keyword(s):

Cell Differentiation ◽

Neuronal Differentiation ◽

Rod Photoreceptor ◽

Bhlh Gene ◽

Basic Helix Loop Helix ◽

Helix Loop Helix ◽

Differentiated Cells ◽

Loop Region ◽

The Family ◽

Enhancer Of Split

We have isolated the basic helix-loop-helix (bHLH) gene Hes6, a novel member of the family of mammalian homologues of Drosophila hairy and Enhancer of split. Hes6 is expressed by both undifferentiated and differentiated cells, unlike Hes1, which is expressed only by the former cells. Hes6 alone does not bind to the DNA but suppresses Hes1 from repressing transcription. In addition, Hes6 suppresses Hes1 from inhibiting Mash1-E47 heterodimer and thereby enables Mash1 and E47 to upregulate transcription in the presence of Hes1. Furthermore, misexpression of Hes6 with retrovirus in the developing retina promotes rod photoreceptor differentiation, like Mash1, in sharp contrast to Hes1, which inhibits cell differentiation. These results suggest that Hes6 is an inhibitor of Hes1, supports Mash1 activity and promotes cell differentiation. Mutation analysis revealed that Hes1- and Hes6-specific functions are, at least in part, interchangeable by alteration of the loop region, suggesting that the loop is not simply a nonfunctional spacer but plays an important role in the specific functions.

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