scholarly journals An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

Development ◽  
2020 ◽  
Vol 147 (20) ◽  
pp. dev187856
Author(s):  
Veena Kinare ◽  
Archana Iyer ◽  
Hari Padmanabhan ◽  
Geeta Godbole ◽  
Tooba Khan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regional Identity ◽  
Wing Disc ◽  
Cell Fate Specification ◽  
Dimerization Domain ◽  
Molecular Identity ◽  
Evolutionarily Conserved ◽  
Chimeric Construct ◽  
Single Transcript ◽  
Tetrameric Complex

ABSTRACTThe protein co-factor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain.

scholarly journals An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

2020 ◽  
Author(s):  
Veena Kinare ◽  
Archana Iyer ◽  
Hari Padmanabhan ◽  
Geeta Godbole ◽  
Tooba Khan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regional Identity ◽  
Wing Disc ◽  
Dimerization Domain ◽  
Evolutionarily Conserved ◽  
Chimeric Construct ◽  
Summary Statement ◽  
Hippocampal Development ◽  
Single Transcript ◽  
Tetrameric Complex

AbstractProtein cofactor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain.Summary statementSimilar to an Apterous-Chip mechanism that patterns the Drosophila wing blade, interaction between mammalian orthologs Lhx2 and Ldb1 regulates multiple aspects of hippocampal development in the mouse.

scholarly journals CFP-1 interacts with HDAC1/2 complexes inC. elegansdevelopment

2018 ◽  
Author(s):  
Bharat Pokhrel ◽  
Yannic Chen ◽  
Jonathan Joseph Biro
Keyword(s):  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Dependent Manner ◽  
Cell Fate Specification ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Epigenetic Regulator ◽  
Inducible Genes

AbstractCFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in humans andC. elegans. This conserved epigenetic regulator is a part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 inC. elegans. Previous studies have indicated the importance ofcfp-1in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action ofcfp-1is well understood at the organismal level. To further investigate the function of CFP-1, we have characterisedC. elegansCOMPASS mutantscfp-1(tm6369)andset-2(bn129). We found that bothcfp-1andset-2play an important role in the regulation of fertility and development of the organism. Furthermore, we found that bothcfp-1andset-2are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found thatcfp-1but notset-2genetically interacts with Histone Deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally we found thatcfp-1andset-2acts on a separate pathways to regulate fertility and development ofC. elegans. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within COMPASS complex. We propose that CFP-1 could cooperate with COMPASS complex and/or HDAC1/2 in a context dependent manner.

scholarly journals RBP-Jκ-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development

2006 ◽  
Vol 26 (13) ◽  
pp. 4769-4774 ◽  
Author(s):  
Céline Souilhol ◽  
Sarah Cormier ◽  
Kenji Tanigaki ◽  
Charles Babinet ◽  
Michel Cohen-Tannoudji
Keyword(s):  
Embryonic Development ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Preimplantation Embryos ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Evolutionarily Conserved

ABSTRACT The Notch signaling pathway is an evolutionarily conserved signaling system which has been shown to be essential in cell fate specification and in numerous aspects of embryonic development in all metazoans thus far studied. We recently demonstrated that several components of the Notch signaling pathway, including the four Notch receptors and their five ligands known in mammals, are expressed in mouse oocytes, in mouse preimplantation embryos, or both. This suggested a possible implication of the Notch pathway in the first cell fate specification of the dividing mouse embryo, which results in the formation of the blastocyst. To address this issue directly, we generated zygotes in which both the maternal and the zygotic expression of Rbpsuh, a key element of the core Notch signaling pathway, were abrogated. We find that such zygotes give rise to blastocysts which implant and develop normally. Nevertheless, after gastrulation, these embryos die around midgestation, similarly to Rbpsuh-null mutants. This demonstrates that the RBP-Jκ-dependent pathway, otherwise called the canonical Notch pathway, is dispensable for blastocyst morphogenesis and the establishment of the three germ layers, ectoderm, endoderm, and mesoderm. These results are discussed in the light of recent observations which have challenged this conclusion.

Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1673-1682 ◽  
Author(s):  
M. Gho ◽  
M. Lecourtois ◽  
G. Geraud ◽  
J.W. Posakony ◽  
F. Schweisguth
Keyword(s):  
Subcellular Localization ◽  
Cell Fate ◽  
Sense Organ ◽  
Wing Disc ◽  
Tissue Polarity ◽  
Cell Fate Decisions ◽  
Suppressor Of Hairless ◽  
Evolutionarily Conserved ◽  
Disc Cells ◽  
Sensory Organ Precursor

During imaginal development of Drosophila, Suppressor of Hairless [Su(H)], an evolutionarily conserved transcription factor that mediates intracellular signalling by the Notch (N) receptor, controls successive alternative cell fate decisions leading to the differentiation of multicellular sensory organs. We describe here the distribution of the Su(H) protein in the wing disc epithelium throughout development of adult sense organs. Su(H) was found to be evenly distributed in the nuclei of all imaginal disc cells during sensory organ precursor cells selection. Thus differential expression and/or subcellular localization of Su(H) is not essential for its function. Soon after division of the pIIa secondary precursor cell, Su(H) specifically accumulates in the nucleus of the future socket cell. At the onset of differentiation of the socket cell, Su(H) is also detected in the cytoplasm. In this differentiating cell, N and deltex participate in the cytoplasmic retention of Su(H). Still, Su(H) does not colocalize with N at the apical-lateral membranes. These observations suggest that N regulates in an indirect manner the cytoplasmic localization of Su(H) in the socket cell. Finally, the pIIb, shaft and socket cells are found to adopt invariant positions along the anteroposterior axis of the notum. This raises the possibility that tissue-polarity biases these N-mediated cell fate choices.

Lineage-tracing cells born in different domains along the PD axis of the developing Drosophila leg

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3823-3830 ◽  
Author(s):  
K. Weigmann ◽  
S.M. Cohen
Keyword(s):  
Cell Fate ◽  
Imaginal Discs ◽  
Wing Disc ◽  
Lineage Tracing ◽  
Ligand Concentration ◽  
Signaling Proteins ◽  
Cell Fate Specification ◽  
Morphogen Gradients ◽  
Fate Specification ◽  
Lower Ligand

Patterning of the developing limbs by the secreted signaling proteins Wingless, Hedgehog and Dpp takes place while the imaginal discs are growing rapidly. Cells born in regions of high ligand concentration may be displaced through growth to regions of lower ligand concentration. We have used a novel lineage-tagging method to address the reversibility of cell fate specification by morphogen gradients. We find that responses to Hedgehog and Dpp in the wing disc are readily reversible. In the leg, we find that cells readily adopt more distal fates, but do not normally shift from distal to proximal fate. However, they can do so if given a growth advantage. These results indicate that cell fate specification by morphogen gradients remains largely reversible while the imaginal discs grow. In other systems, where growth and patterning are uncoupled, nonreversible specification events or ‘ratchet’ effects may be of functional significance.

scholarly journals The developmental origins of Notch-driven intrahepatic bile duct disorders

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Anabel Martinez Lyons ◽  
Luke Boulter
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Intrahepatic Bile Duct ◽  
Cell Communication ◽  
Notch Signaling Pathway ◽  
Cell Fate Specification ◽  
Evolutionarily Conserved ◽  
Embryonic Life

ABSTRACT The Notch signaling pathway is an evolutionarily conserved mechanism of cell–cell communication that mediates cellular proliferation, cell fate specification, and maintenance of stem and progenitor cell populations. In the vertebrate liver, an absence of Notch signaling results in failure to form bile ducts, a complex tubular network that radiates throughout the liver, which, in healthy individuals, transports bile from the liver into the bowel. Loss of a functional biliary network through congenital malformations during development results in cholestasis and necessitates liver transplantation. Here, we examine to what extent Notch signaling is necessary throughout embryonic life to initiate the proliferation and specification of biliary cells and concentrate on the animal and human models that have been used to define how perturbations in this signaling pathway result in developmental liver disorders.

Musashi: a translational regulator of cell fate

2002 ◽  
Vol 115 (7) ◽  
pp. 1355-1359 ◽  
Author(s):  
Hideyuki Okano ◽  
Takao Imai ◽  
Masataka Okabe
Keyword(s):  
Cell Fate ◽  
Translational Regulation ◽  
Rna Binding ◽  
Notch Signalling ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Evolutionarily Conserved ◽  
Protein Functions ◽  
Neural Cell Fate ◽  
Stem Cell State

Transcription is thought to have a major role in the regulation of cell fate; the importance of translational regulation in this process has been less certain. Recent findings demonstrate that translational regulation contributes to cell-fate specification. The evolutionarily conserved, neural RNA-binding protein Musashi, for example, controls neural cell fate. The protein functions in maintenance of the stem-cell state, differentiation, and tumorigenesis by repressing translation of particular mRNAs. In mammals it might play an important role in activating Notch signalling by repressing translation of the Notch inhibitor m-Numb.

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