The role of Phox2b in synchronizing pan-neuronal and type-specific aspects of neurogenesis

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5241-5253
Author(s):  
Véronique Dubreuil ◽  
Marie-Rose Hirsch ◽  
Caroline Jouve ◽  
Jean-François Brunet ◽  
Christo Goridis
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Neuronal Differentiation ◽  
Genetic Interactions ◽  
Homeodomain Transcription Factor ◽  
Dual Action ◽  
Separate Pathway ◽  
Neuronal Subtype ◽  
Necessary And Sufficient

Within the developing vertebrate nervous system, specific subclasses of neurons are produced in vastly different numbers at defined times and locations. This implies the concomitant activation of a program that controls pan-neuronal differentiation and of a program that specifies neuronal subtype identity, but how these programs are coordinated in time and space is not well understood. Our previous loss- and gain-of-function studies have defined Phox2b as a homeodomain transcription factor that coordinately regulates generic and type-specific neuronal properties. It is necessary and sufficient to impose differentiation towards a branchio- and viscero-motoneuronal phenotype and at the same time promotes generic neuronal differentiation. We have examined the underlying genetic interactions. We show thatPhox2b has a dual action on pan-neuronal differentiation. It upregulates the expression of proneural genes (Ngn2) when expressed alone and upregulates the expression of Mash1 when expressed in combination with Nkx2.2. By a separate pathway, Phox2brepresses expression of the inhibitors of neurogenesis Hes5 andId2. The role of Phox2b in the specification of neuronal subtype identity appears to depend in part on its capacity to act as a patterning gene in the progenitor domain. Phox2b misexpression represses the Pax6 and Olig2 genes, which should inhibit a branchiomotor fate, and induces Nkx6.1 and Nkx6.2, which are expressed in branchiomotor progenitors. We further show that Phox2b behaves like a transcriptional activator in the promotion of both, generic neuronal differentiation and expression of the motoneuronal marker Islet1. These results provide insights into the mechanisms by which a homeodomain transcription factor through interaction with other factors controls both generic and type-specific features of neuronal differentiation.

Novel Homeodomain Transcription Factor Nkx2.2 in the Brain Tumor Development

2020 ◽  
Vol 20 (5) ◽  
pp. 335-340 ◽  
Author(s):  
Mubeena P.M. Mariyath ◽  
Mehdi H. Shahi ◽  
Shirin Farheen ◽  
Mohd Tayyab ◽  
Nabeela Khanam ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Tumor Development ◽  
Normal Growth ◽  
Vital Role ◽  
Homeodomain Transcription Factor ◽  
Shh Pathway ◽  
Potential Biomarker

Background: Complex central nervous system (CNS) is made up of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage. MBP + oligodendrocytes are differentiated from progenitor cells which express Olig2. Nx2.2 is co-expressed with Olig2 in oligodendrocytes and is essential for later stage of oligodendrocyte maturation. Objective: This review paper explores the potential role of Nkx2.2 transcription factor in glioblastoma development. Conclusion: Shh pathway plays a vital role in oligodendrocytes differentiation and Nkx2.2 transcription factor is essential for oligodendrocytes differentiation and maturation. Intriguingly, down regulation of Nkx2.2 transcription factor with aberrant Shh signaling pathway is reported in glioma samples. So here it is suggested that Nkx2.2 expression pattern could be used as a potential biomarker for the early diagnosis of glioma.

Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells

2000 ◽  
Vol 113 (15) ◽  
pp. 2705-2713
Author(s):  
K. Sawada ◽  
Y. Konishi ◽  
M. Tominaga ◽  
Y. Watanabe ◽  
J. Hirano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Mammalian Cells ◽  
Homeobox Gene ◽  
S Phase ◽  
Bhlh Transcription Factor ◽  
Spemann Organizer

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.

scholarly journals Drosophila Zic family member odd-paired is needed for adult post-ecdysis maturation

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190245
Author(s):  
Eléanor Simon ◽  
Sergio Fernández de la Puebla ◽  
Isabel Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Family Member ◽  
Ectopic Expression ◽  
Functional Conservation ◽  
The Central Nervous System ◽  
Behavioural Sequence

Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster , the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologue Zic2 , in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.

Glial differentiation and the Gcm pathway

2007 ◽  
Vol 3 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Laurent Soustelle ◽  
Angela Giangrande
Keyword(s):  
Developmental Biology ◽  
Nervous System ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Stem Cell Differentiation ◽  
Molecular Pathways ◽  
Glial Differentiation ◽  
Cell Diversity ◽  
Necessary And Sufficient

AbstractOne of the most challenging issues in developmental biology is to understand how cell diversity is generated. The Drosophila nervous system provides a model of choice for unraveling this process. First, many neural stem cells and lineages have been identified. Second, major molecular pathways involved in neural development and associated mutations have been characterized extensively in recent years. In this review, we focus on the cellular and molecular mechanisms underlying the generation of glia. This cell population relies on the expression of gcm fate determinant, which is necessary and sufficient to induce glial differentiation. We also discuss the recently identified role of gcm genes in Drosophila melanogaster and vertebrate neurogenesis. Finally, we will consider the Gcm pathway in the context of neural stem cell differentiation.

scholarly journals MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 609-620 ◽  
Author(s):  
L. Lo ◽  
M.C. Tiveron ◽  
D.J. Anderson
Keyword(s):  
Transcription Factor ◽  
Neuronal Differentiation ◽  
Large Fraction ◽  
Constitutive Expression ◽  
Neuronal Morphology ◽  
Bone Morphogenetic Protein 2 ◽  
General Idea ◽  
Homeodomain Transcription Factor ◽  
Neuronal Markers ◽  
Neuronal Identity

We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and consequent autonomic neuronal differentiation. We now show that BMP2 also induces expression of the paired homeodomain transcription factor Phox2a, and the GDNF/NTN signalling receptor tyrosine kinase c-RET. Constitutive expression of MASH1 in NCSCs from a retroviral vector, in the absence of exogenous BMP2, induces expression of both Phox2a and c-RET in a large fraction of infected colonies, and also promotes morphological neuronal differentiation and expression of pan-neuronal markers. In vivo, expression of Phox2a in autonomic ganglia is strongly reduced in Mash1 −/− embryos. These loss- and gain-of-function data suggest that MASH1 positively regulates expression of Phox2a, either directly or indirectly. Constitutive expression of Phox2a, by contrast to MASH1, fails to induce expression of neuronal markers or a neuronal morphology, but does induce expression of c-RET. These data suggest that MASH1 couples expression of pan-neuronal and subtype-specific components of autonomic neuronal identity, and support the general idea that identity is established by combining subprograms involving cascades of transcription factors, which specify distinct components of neuronal phenotype.

Bioinformatic Analysis of Transcriptional Regulation by Nur77 in Central Nervous System and Immune System

2021 ◽  
Author(s):  
Montserrat Olivares Costa ◽  
Fernando Faunes ◽  
María Estela Andrés
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Immune Cells ◽  
Binding Sites ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Neuronal Stem Cells

Abstract ObjectiveThe objectives of this work were to find genes regulated by Nur77 in neurons and to evaluate the possible common role of this transcription factor in neurons and lymphatic cells using published experimentally generated databases of ChIP-Seq and a microarray. We also characterized Nur77 binding throughout the genome. ResultsWe identified 113 Nur77 target genes in neuronal stem cells and 116 in neuronal cells. Cell adhesion and anchoring processes emerged as regulated by Nur77 in neurons and lymphatic cells. We found 9 common genes regulated by Nur77. Finally, we described a significant distribution of Nur77 binding sites in strong enhancers and active promoters. This work is a first step to understand the role of Nur77 and its common targets in neurons and immune cells.

scholarly journals S08-10 The role of homeodomain transcription factor HNF1B in nephrogenesis

2009 ◽  
Vol 126 ◽  
pp. S34
Author(s):  
Gerhart U. Ryffel ◽  
Magdalena Roose ◽  
Kathrin Sauert ◽  
Christiane Drews ◽  
Christoph Waldner
Keyword(s):  
Transcription Factor ◽  
Homeodomain Transcription Factor

scholarly journals Essential role of spi-1–like (spi-1l) in zebrafish myeloid cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 2038-2046 ◽  
Author(s):  
Alex Bukrinsky ◽  
Kevin J. P. Griffin ◽  
Yan Zhao ◽  
Shuo Lin ◽  
Utpal Banerjee
Keyword(s):  
Functional Analysis ◽  
Transcription Factor ◽  
Cell Differentiation ◽  
Essential Role ◽  
Critical Role ◽  
Myeloid Cell ◽  
Myeloid Differentiation ◽  
Adult Kidney ◽  
Necessary And Sufficient

The ETS protein Spi-1/Pu.1 plays a pivotal and widespread role throughout hematopoiesis in many species. This study describes the identification, characterization, and functional analysis of a new zebrafish spi transcription factor spi-1–like (spi-1l) that is expressed in primitive myeloid cells, erythro-myelo progenitor cells, and in the adult kidney. Spi-1l functions genetically downstream of etsrp, scl, and spi-1/pu.1 in myeloid differentiation. Spi-1l is coexpressed in a subset of spi-1/pu.1 cells and its function is necessary and sufficient for macrophage and granulocyte differentiation. These results establish a critical role for spi-1l in zebrafish myeloid cell differentiation.

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