scholarly journals The basic helix-loop-helix transcription factors LIN-32 and HLH-2 function together in multiple steps of a C. elegans neuronal sublineage

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5415-5426 ◽  
Author(s):  
D.S. Portman ◽  
S.W. Emmons
Keyword(s):  
Transcription Factors ◽  
Neuronal Development ◽  
Cell Types ◽  
Gene Encoding ◽  
Structural Cell ◽  
C Elegans ◽  
Helix Loop Helix ◽  
Bhlh Genes

bHLH transcription factors function in neuronal development in organisms as diverse as worms and vertebrates. In the C. elegans male tail, a neuronal sublineage clonally gives rise to the three cell types (two neurons and a structural cell) of each sensory ray. We show here that the bHLH genes lin-32 and hlh-2 are necessary for the specification of multiple cell fates within this sublineage, and for the proper elaboration of differentiated cell characteristics. Mutations in lin-32, a member of the atonal family, can cause failures at each of these steps, resulting in the formation of rays that lack fully-differentiated neurons, neurons that lack cognate rays, and ray cells defective in the number and morphology of their processes. Mutations in hlh-2, the gene encoding the C. elegans E/daughterless ortholog, enhance the ray defects caused by lin-32 mutations. In vitro, LIN-32 can heterodimerize with HLH-2 and bind to an E-box-containing probe. Mutations in these genes interfere with this activity in a manner consistent with the degree of ray defects observed in vivo. We propose that LIN-32 and HLH-2 function as a heterodimer to activate different sets of targets, at multiple steps in the ray sublineage. During ray development, lin-32 performs roles of proneural, neuronal precursor, and differentiation genes of other systems.

Identification of Key Cellular Regulators That Interact with Id1 To Control Hematopoietic Stem Cell Behavior.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1319-1319
Author(s):  
Vladimir Jankovic ◽  
Alessia Ciarrocchi ◽  
Tony DeBlasio ◽  
Robert Benezra ◽  
Stephen D. Nimer
Keyword(s):  
Transcription Factors ◽  
Transcriptional Repression ◽  
Genetic Interaction ◽  
Dominant Negative ◽  
Double Knockout ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Helix Loop Helix

Abstract The ability of hematopoietic stem cells to tightly regulate the transition from relative quiescence and self-renewal to the transiently amplifying, differentiating progenitor fate is critical for HSC homeostasis as well as their regenerative capacity. We have recently described the diminished frequency and rapid exhaustion of HSC self-renewal capacity in the absence of the dominant negative helix-loop-helix molecule Id1. Furthermore, Id1 null HSCs have an increased rate of cycling, coupled with accelerated myeloid commitment both in vivo and in vitro. This is reflected in the elevated expression of myelo-erythroid transcription factors (c/EBPalpha and GATA1) within the Lin−c-kit+Sca-1+ population - “myeloid priming”. The major targets of Id1 mediated transcriptional repression are the ubiquitous E protein E2A as well as Ets transcription factors (Ets1 and Ets2). We hypothesized that the unrestrained activity of these and/or other targets of Id1 transcriptional repression leads to premature HSC commitment in Id1 null animals. Indeed, we show that HSC differentiation in culture can be delayed by transduction of E2A directed shRNA specifically in Id1 null, but not in wild-type Id1 expressing cells. This indicates an abnormal E2A activity in Id1 null HSCs that could be responsible for their increased differentiation status. To further define the transcriptional deregulation in Id1 null HSCs, we have used the Affymetrix microarray technology. We observed ~3 fold increased expression of the CDK inhibitor p21 in freshly isolated Id1 null HSCs and have confirmed this result by multiple independent qPCR measurements. The transcriptional induction of p21 by E2A as well as its repression by Id1 have been well established. Therefore, the observed p21 induction could be explained by the elevated level of E2A activity in HSCs in the absence of Id1 expression. To explore the functional significance of Id1 mediated p21 regulation in HSCs, we have generated p21/Id1 double knockout animals. Surprisingly, despite its reported function in restricting the cell cycle entry of normal HSCs, we show that in the context of Id1 loss, p21 expression is required for the accelerated HSC cycling, and unlike Id1 single null HSCs, p21/Id1 double knockout HSCs do not show accelerated myeloid differentiation in culture. Therefore, we propose that Id1 actively represses E2A activity in HSCs, as well as the induction of p21, which could be an important component of the HSC commitment program. Further studies will be presented defining the in vivo relevance of the Id1/p21 genetic interaction for HSC growth and differentiation.

scholarly journals The role of SOX proteins in normal pituitary development

2008 ◽  
Vol 200 (3) ◽  
pp. 245-258 ◽  
Author(s):  
Kyriaki S Alatzoglou ◽  
Daniel Kelberman ◽  
Mehul T Dattani
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Cell Types ◽  
Transgenic Animal ◽  
Developmental Abnormalities ◽  
Pituitary Development ◽  
Organ Systems ◽  
Sox Proteins

Pituitary development is a complex process that depends on the co-ordinated spatial and temporal expression of transcription factors and signalling molecules that culminates in the formation of a complex organ that secretes six hormones from five different cell types. Given the fact that all distinct hormone producing cells arise from a common ectodermal primordium, the patterning, architecture and plasticity of the gland is impressive. Among the transcription factors involved in the early steps of pituitary organogenesis are SOX2 and SOX3, members of the SOX family that are emerging as key players in many developmental processes. Studies in vitro and in vivo in transgenic animal models have helped to elucidate their expression patterns and roles in the developing hypothalamo–pituitary region. It has been demonstrated that they may be involved in pituitary development either directly, through shaping of Rathke's pouch, or indirectly affecting signalling from the diencephalon. Their role has been further underlined by the pleiotropic effects of their mutations in humans that range from isolated hormone deficiencies to panhypopituitarism and developmental abnormalities affecting many organ systems. However, the exact mechanism of action of SOX proteins, their downstream targets and their interplay within the extensive network that regulates pituitary development is still the subject of a growing number of studies. The elucidation of their role is crucial for the understanding of a number of processes that range from developmental mechanisms to disease phenotypes and tumorigenesis.

scholarly journals Propofol impairs specification of retinal cell types in zebrafish by inhibiting Zisp-mediated Noggin-1 palmitoylation and trafficking

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments

Abstract Background Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. Methods The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2′-deoxyuridine labeling, co-immunoprecipitation, and acyl–biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types. Results Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate. Conclusions Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

scholarly journals Homo- and heterodimerization of bHLH transcription factors balance stemness and bipotential differentiation

2019 ◽  
Author(s):  
Aleix Puig-Barbé ◽  
Joaquín de Navascués
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Adult Stem Cells ◽  
Cell Types ◽  
E Proteins ◽  
Self Renewal ◽  
Helix Loop Helix ◽  
Mechanism Of Interaction ◽  
Bhlh Transcription Factors

ABSTRACTMultipotent adult stem cells must balance self-renewal with differentiation into various mature cell types. How this activity is molecularly regulated is poorly understood. By using genetic and molecular analyses in vivo, we show that a small network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential differentiation in the Drosophila adult intestine. We find that homodimers of Daughterless (Da, homolog to mammalian E proteins) maintain the self-renewal of intestinal stem cells and antagonise the activity of heterodimers of Da and Scute (Sc, homolog to ASCL and known to promote intestinal secretory differentiation). We find a novel role for the HLH factor Extramacrochaetae (Emc, homolog to Id proteins), titrating Da and Sc to promote absorptive differentiation. We further show that Emc prevents committed absorptive progenitors from de-differentiating, revealing the plasticity of these cells. This mechanism of interaction partner-switching enables the active maintenance of stemness, but primes stem cells for differentiation along two alternative fates. Such regulatory logic could be recapitulated in other bipotent stem cell systems.

The role of transcription factors, chromatin structure and DNA replication in 5 S RNA gene regulation

1994 ◽  
Vol 107 (8) ◽  
pp. 2055-2063 ◽  
Author(s):  
A.P. Wolffe
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Protein Interactions ◽  
Multigene Family ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Eukaryotic Genes ◽  
Rna Genes

Differential expression of the oocyte and somatic 5 S RNA genes during Xenopus development can be explained by changes in transcription factor and histone interactions with the two types of gene. Both factors and histones bind 5 S RNA genes with specificity. Protein-protein interactions determine the stability of potentially transcriptionally active or repressed nucleoprotein complexes. A decline in transcription factor abundance, differential binding of transcription factors to oocyte and somatic 5 S genes, and increased competition with the histones for association with DNA during early embryogenesis, can account for the developmental decision to selectively repress the oocyte genes, while retaining the somatic genes in the transcriptionally active state. The 5 S ribosomal genes of Xenopus are perhaps the simplest eukaryotic genes to show regulated expression during development. A large multigene family (oocyte 5 S DNA) is transcriptionally active in oocytes but is repressed in somatic cells, whereas a small multigene family (somatic 5 S DNA) is active in both cell types. A potential molecular mechanism to explain the developmental switch that turns off oocyte 5 S DNA transcription has been experimentally reconstructed in vitro and more recently tested in vivo. Central to this mechanism is the specific association of both transcription factors and histones with 5 S RNA genes. How the interplay of histones and transcription factors is thought to affect transcription, and how their respective contributions might change during development from an oocyte, to an embryo and eventually to a somatic cell is the focus of this review.

Propofol Impairs Specification of Retinal Cell Types in Zebrafish by Inhibiting Zisp-mediated Noggin-1 Palmitoylation and Trafficking

2020 ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Lizhu Hu ◽  
Delong Wang ◽  
Ruiting Wang ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Cell Formation ◽  
Cognitive Disorders ◽  
Cell Types ◽  
Retinal Cell ◽  
Soluble Form ◽  
In Vivo Experiments ◽  
Developing Neurons

Abstract Background: Propofol can have adverse effects on developing neurons, leading to cognitive disorders. However, the mechanism remains elusive. Here, we aimed to investigate the effect and molecular mechanism of propofol on neuronal development in zebrafish. Methods: The effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, Whole-mount in situ hybridization and immunohistochemistry, quantitative real-time PCR, TUNEL, EdU, Co-Immunoprecipitation and acyl–biotin exchange (ABE) labeling method were carried out to demonstrate the potential mechanisms of propofol-mediated zisp expression and specification of retinal cell types.Results: Propofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through inhibition of Zisp expression. Furthermore, Zisp promoted the secretion of a soluble form and the stabilization of a membrane-associated form of Noggin-1, a specific palmitoylation substrate.Conclusions: Propofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.

scholarly journals Two differentially expressed interleukin-11 receptor genes in the mouse genome

1996 ◽  
Vol 320 (2) ◽  
pp. 359-363 ◽  
Author(s):  
Petra BILINSKI ◽  
Mark A. HALL ◽  
Herbert NEUHAUS ◽  
Cornelia GISSEL ◽  
John K. HEATH ◽  
...  
Keyword(s):  
Mouse Genome ◽  
Amino Acid Level ◽  
Cell Types ◽  
Ligand Specificity ◽  
Gene Encoding ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Interleukin 11

Interleukin-11 (IL-11) is a multifunctional cytokine involved in the regulation of cell proliferation and differentiation in a variety of cell types and tissues in vitro and in vivo. The effects of IL-11 were shown to be mediated by the IL-11 receptor (hereafter referred to as IL-11Rα), which is a ligand-binding subunit and provides ligand specificity in a functional multimeric signal-transduction complex with gp130. Here we show that the mouse genome contains a second gene encoding an IL-11-binding protein, referred to as IL-11Rβ. The structure of the IL-11Rβ gene is highly similar to that of IL-11Rα, and IL-11Rβ exhibits 99% sequence identity with IL-11Rα at the amino acid level. IL-11Rβ is co-expressed with IL-11Rα, albeit at lower levels, in embryos and in various adult tissues. IL-11Rβ transcripts are abundant in testis, and, in contrast with IL-11Rα, absent from skeletal muscle. IL-11Rβ expressed in vitro binds IL-11 with high affinity, suggesting that the mouse genome contains a second functional IL-11R.

scholarly journals Basic Helix-Loop-Helix Transcription Factor Heterocomplex of Yas1p and Yas2p Regulates Cytochrome P450 Expression in Response to Alkanes in the Yeast Yarrowia lipolytica

2007 ◽  
Vol 6 (4) ◽  
pp. 734-743 ◽  
Author(s):  
Setsu Endoh-Yamagami ◽  
Kiyoshi Hirakawa ◽  
Daisuke Morioka ◽  
Ryouichi Fukuda ◽  
Akinori Ohta
Keyword(s):  
Cytochrome P450 ◽  
Transcription Factors ◽  
Yarrowia Lipolytica ◽  
Bhlh Protein ◽  
Genome Database ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Transcription Factors

ABSTRACT The expression of the ALK1 gene, which encodes cytochrome P450, catalyzing the first step of alkane oxidation in the alkane-assimilating yeast Yarrowia lipolytica, is highly regulated and can be induced by alkanes. Previously, we identified a cis-acting element (alkane-responsive element 1 [ARE1]) in the ALK1 promoter. We showed that a basic helix-loop-helix (bHLH) protein, Yas1p, binds to ARE1 in vivo and mediates alkane-dependent transcription induction. Yas1p, however, does not bind to ARE1 by itself in vitro, suggesting that Yas1p requires another bHLH protein partner for its DNA binding, as many bHLH transcription factors function by forming heterodimers. To identify such a binding partner of Yas1p, here we screened open reading frames encoding proteins with the bHLH motif from the Y. lipolytica genome database and identified the YAS2 gene. The deletion of the YAS2 gene abolished the alkane-responsive induction of ALK1 transcription and the growth of the yeast on alkanes. We revealed that Yas2p has transactivation activity. Furthermore, Yas1p and Yas2p formed a protein complex that was required for the binding of these proteins to ARE1. These findings allow us to postulate a model in which bHLH transcription factors Yas1p and Yas2p form a heterocomplex and mediate the transcription induction in response to alkanes.

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