Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 555-566 ◽  
Author(s):  
X.W. Yang ◽  
R. Zhong ◽  
N. Heintz
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Granule Cell ◽  
Ventricular Zone ◽  
Critical Role ◽  
Neuronal Cell ◽  
Developing Brain ◽  
Granule Neurons ◽  
Cell Specification ◽  
Rhombic Lip

The creation of specific neuronal cell types within the developing brain is a critical and unsolved biological problem. Precedent from invertebrate development, and from vertebrate myogenesis and lymphogenesis, has established that cell specification often involves transcription factors that are expressed throughout the differentiation of a given cell type. In this study, we have identified in Zn2+ finger transcription factor RU49 as a definitive marker for the cerebellar granule neuron lineage. Thus, RU49 is expressed in the earliest granule cell progenitors at the rhombic lip as they separate from the ventricular zone of the neural tube to generate a secondary proliferative matrix, and it continues to be expressed in differentiating and mature granule neurons. Proliferating granule cell progenitors isolated from the rhombic lip at E14 or from the external germinal layer at P6 continue to express RU49 in vitro. Both the olfactory bulb and dentate gyrus granule cell lineages also express this factor as they are generated with the developing brain. RU49 binds a novel bipartite DNA-binding element in a manner consistent with chemical rules governing the DNA-binding specificity of this class of transcription factor. The novel biochemical properties of RU49 and its restricted expression within the three lineages of CNS granule neurons suggest that RU49 may play a critical role in their specification. Furthermore, these results raise the interesting possibility that the generation of these three neuronal populations to form displaced germinative zones within the developing brain may reflect their use of a common developmental mechanism involving RU49.

scholarly journals Contrasting DNA-binding behaviour by ISL1 and LHX3 underpins differential gene targeting in neuronal cell specification

2020 ◽  
pp. 100043
Author(s):  
Ngaio C. Smith ◽  
Lorna E. Wilkinson-White ◽  
Ann H.Y. Kwan ◽  
Jill Trewhella ◽  
Jacqueline M. Matthews
Keyword(s):  
Dna Binding ◽  
Gene Targeting ◽  
Neuronal Cell ◽  
Cell Specification ◽  
Differential Gene ◽  
Binding Behaviour

scholarly journals Olig3 regulates early cerebellar development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elijah D Lowenstein ◽  
Aleksandra Rusanova ◽  
Jonas Stelzer ◽  
Marc Hernaiz-Llorens ◽  
Adrian E Schroer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Purkinje Cell ◽  
Ventricular Zone ◽  
Cerebellar Development ◽  
Brain Functions ◽  
Key Factor ◽  
Progenitor Cell Proliferation ◽  
Molecular Machinery ◽  
Neuronal Types ◽  
Rhombic Lip

The mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition, and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones in mice. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that suppresses the Purkinje cell differentiation program. Our work thus defines Olig3 as a key factor in early cerebellar development.

scholarly journals Detection in non-erythroid cells of a factor with the binding characteristics of the erythroid cell transcription factor EF1

1990 ◽  
Vol 269 (2) ◽  
pp. 543-545
Author(s):  
N D Perkins ◽  
K H Orchard ◽  
M L K Collins ◽  
D S Latchman ◽  
G H Goodwin
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Critical Role ◽  
Cell Types ◽  
Erythroid Cell ◽  
Erythroid Cells ◽  
First Report ◽  
Binding Characteristics

The erythroid transcription factor erythroid factor-1 (EF1) plays a critical role in the transcription of erythroid-specific genes. Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of EF1 at low abundance in a wide variety of non-erythroid cell types. This is the first report of an EF1-like activity in non-erythroid cells and indicates that this factor may play a role in the regulation of genes expressed in such cells.

scholarly journals The TAL1/SCL Transcription Factor Regulates Cell Cycle Progression and Proliferation in Differentiating Murine Bone Marrow Monocyte Precursors

2010 ◽  
Vol 30 (9) ◽  
pp. 2181-2192 ◽  
Author(s):  
Soumyadeep Dey ◽  
David J. Curtis ◽  
Stephen M. Jane ◽  
Stephen J. Brandt
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Transcription Factor ◽  
Dna Binding ◽  
Cell Cycle Progression ◽  
Ex Vivo ◽  
Critical Role ◽  
Sequence Element ◽  
Cycle Progression ◽  
Murine Bone Marrow

ABSTRACT Monocytopoiesis involves the stepwise differentiation in the bone marrow (BM) of common myeloid precursors (CMPs) to monocytes. The basic helix-loop-helix transcription factor TAL1/SCL plays a critical role in other hematopoietic lineages, and while it had been reported to be expressed by BM-derived macrophages, its role in monocytopoiesis had not been elucidated. Using cell explant models of monocyte/macrophage (MM) differentiation, one originating with CMPs and the other from more committed precursors, we characterized the phenotypic and molecular consequences of inactivation of Tal1 expression ex vivo. While Tal1 knockout had minimal effects on cell survival and slightly accelerated terminal differentiation, it profoundly inhibited cell proliferation and decreased entry into and traversal of the G1 and S phases. In conjunction, steady-state levels of p16(Ink4a) mRNA were increased and those of Gata2 mRNA decreased. Chromatin immunoprecipitation analysis demonstrated the association of Tal1 and E47, one of its E protein DNA-binding partners, with an E box-GATA sequence element in intron 4 of the Gata2 gene and with three E boxes upstream of p16(Ink4a). Finally, wild-type Tal1, but not a DNA binding-defective mutant, rescued the proliferative defect in Tal1-null MM precursors. These results document the importance of this transcription factor in cell cycle progression and proliferation during monocytopoiesis and the requirement for direct DNA binding in these processes.

scholarly journals Autoactivation by a Candida glabrata copper metalloregulatory transcription factor requires critical minor groove interactions.

1996 ◽  
Vol 16 (2) ◽  
pp. 724-734 ◽  
Author(s):  
K A Koch ◽  
D J Thiele
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Candida Glabrata ◽  
Regulatory Element ◽  
Critical Role ◽  
Minor Groove ◽  
Binding Domain ◽  
Site Directed Mutagenesis ◽  
Binding Studies

Rapid transcriptional autoactivation of the Candida glabrata AMT1 copper metalloregulatory transcription factor gene is essential for survival in the presence of high extracellular copper concentrations. Analysis of the interactions between purified recombinant AMT1 protein and the AMT1 promoter metal regulatory element was carried out by a combination of missing-nucleoside analysis, ethylation interference, site-directed mutagenesis, and quantitative in vitro DNA binding studies. The results of these experiments demonstrate that monomeric AMT1 binds the metal regulatory element with very high affinity and utilizes critical contacts in both the major and minor grooves. A single adenosine residue in the minor groove, conserved in all known yeast Cu metalloregulatory transcription factor DNA binding sites, plays a critical role in both AMT1 DNA binding in vitro and Cu-responsive AMT1 gene transcription in vivo. Furthermore, a mutation in the AMT1 Cu-activated DNA binding domain which converts a single arginine, found in a conserved minor groove binding domain, to lysine markedly reduces AMT1 DNA binding affinity in vitro and results in a severe defect in the ability of C. glabrata cells to mount a protective response against Cu toxicity.

The B-cell and neuronal forms of the octamer-binding protein Oct-2 differ in DNA-binding specificity and functional activity

1991 ◽  
Vol 11 (8) ◽  
pp. 3925-3930
Author(s):  
C L Dent ◽  
K A Lillycrop ◽  
J K Estridge ◽  
N S Thomas ◽  
D S Latchman
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
B Cell ◽  
Functional Activity ◽  
Critical Role ◽  
Neuronal Cell ◽  
Binding Specificity ◽  
Cell Protein ◽  
Mobility Shift ◽  
Dna Binding Specificity

B lymphocytes contain an octamer-binding transcription factor, Oct-2, that is absent in most other cell types and plays a critical role in the B-cell-specific transcription of the immunoglobulin genes. A neuronal form of this protein has also been detected in brain and neuronal cell lines by using a DNA mobility shift assay, and an Oct-2 mRNA is observed in these cells by Northern (RNA) blotting and in situ hybridization. We show that the neuronal form of Oct-2 differs from that found in B cells with respect to both DNA-binding specificity and functional activity. In particular, whereas the B-cell protein activates octamer-containing promoters, the neuronal protein inhibits octamer-mediated gene expression. The possible role of the neuronal form of Oct-2 in the regulation of neuronal gene expression and its relationship to B-cell Oct-2 are discussed.

The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5191-5201 ◽  
Author(s):  
V. Dubreuil ◽  
M. Hirsch ◽  
A. Pattyn ◽  
J. Brunet ◽  
C. Goridis
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Fate ◽  
Motor Neurons ◽  
Ventricular Zone ◽  
Ectopic Expression ◽  
Neuronal Cell ◽  
Cell Cycle Exit ◽  
Neuronal Precursors ◽  
Regulation Of Cell Cycle

In the vertebrate neural tube, cell cycle exit of neuronal progenitors is accompanied by the expression of transcription factors that define their generic and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly understood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic. In the absence of Phox2b, post-mitotic neuronal precursors are not generated in proper numbers. Conversely, forced expression of Phox2b in the embryonic chick spinal cord drives ventricular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation characterised by expression of Islet1 and of the cholinergic transmitter phenotype, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons. These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.

scholarly journals Olig3 acts as a master regulator of cerebellar development

2020 ◽  
Author(s):  
Elijah D. Lowenstein ◽  
Aleksandra Rusanova ◽  
Jonas Stelzer ◽  
Marc Hernaiz-Llorens ◽  
Adrian E. Schroer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ventricular Zone ◽  
Inhibitory Interneuron ◽  
Cerebellar Development ◽  
Brain Functions ◽  
Key Factor ◽  
Progenitor Cell Proliferation ◽  
Molecular Machinery ◽  
Neuronal Types ◽  
Rhombic Lip

AbstractThe mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that we found to impose an inhibitory interneuron identity. Our work thus defines Olig3 as a key factor in cerebellar development.

scholarly journals The B-cell and neuronal forms of the octamer-binding protein Oct-2 differ in DNA-binding specificity and functional activity.

1991 ◽  
Vol 11 (8) ◽  
pp. 3925-3930 ◽  
Author(s):  
C L Dent ◽  
K A Lillycrop ◽  
J K Estridge ◽  
N S Thomas ◽  
D S Latchman
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
B Cell ◽  
Functional Activity ◽  
Critical Role ◽  
Neuronal Cell ◽  
Binding Specificity ◽  
Cell Protein ◽  
Mobility Shift ◽  
Dna Binding Specificity

B lymphocytes contain an octamer-binding transcription factor, Oct-2, that is absent in most other cell types and plays a critical role in the B-cell-specific transcription of the immunoglobulin genes. A neuronal form of this protein has also been detected in brain and neuronal cell lines by using a DNA mobility shift assay, and an Oct-2 mRNA is observed in these cells by Northern (RNA) blotting and in situ hybridization. We show that the neuronal form of Oct-2 differs from that found in B cells with respect to both DNA-binding specificity and functional activity. In particular, whereas the B-cell protein activates octamer-containing promoters, the neuronal protein inhibits octamer-mediated gene expression. The possible role of the neuronal form of Oct-2 in the regulation of neuronal gene expression and its relationship to B-cell Oct-2 are discussed.

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