Synergistic roles of homeodomain proteins UNC-62 homothorax and MLS-2 HMX/NKX in the specification of olfactory neurons in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/iyab133 ◽

2021 ◽

Author(s):

Yi-Wen Hsieh ◽

Rui Xiong ◽

Chiou-Fen Chuang

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Incomplete Penetrance ◽

Homeodomain Protein ◽

Homeodomain Proteins ◽

Complete Penetrance ◽

Late Embryogenesis ◽

Tale Homeodomain ◽

Null Mutants

Abstract General identity of the Caenorhabditis elegans AWC olfactory neuron pair is specified by the OTX/OTD transcription factor CEH-36 and the HMG-box transcription factor SOX-2, followed by asymmetrical differentiation of the pair into two distinct subtypes, default AWCOFF and induced AWCON, through a stochastic signaling event. The HMX/NKX transcription factor MLS-2 regulates the expression of ceh-36 to specify general AWC identity. However, general AWC identity is lost in only one of the two AWC cells in the majority of mls-2 null mutants displaying defective general AWC identity, suggesting that additional transcription factors have a partially overlapping role with MLS-2 in the specification of general AWC identity. Here we identify a role of unc-62, encoding a homothorax/Meis/TALE homeodomain protein, in the specification of general AWC identity. As in mls-2 null mutants, unc-62 null mutants showed an incomplete penetrance in loss of general AWC identity. However, unc-62; mls-2 double mutants display a nearly complete penetrance of identity loss in both AWC cells. Thus, unc-62 and mls-2 have a partially overlapping function in the specification of general AWC identity. Furthermore, our genetic results suggest that mls-2 and unc-62 act cell autonomously in promoting the AWCON subtype. Together, our findings reveal the sequential roles of the unc-62 and mls-2 pair in AWC development, specification of general AWC identity in early embryogenesis and asymmetric differentiation of AWC subtypes in late embryogenesis.

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Expression Pattern, Regulation, and Biological Role of Runt Domain Transcription Factor, run, in Caenorhabditis elegans

Molecular and Cellular Biology ◽

10.1128/mcb.22.2.547-554.2002 ◽

2002 ◽

Vol 22 (2) ◽

pp. 547-554 ◽

Cited By ~ 40

Author(s):

Seunghee Nam ◽

Yun-Hye Jin ◽

Qing-Lin Li ◽

Kwang-Youl Lee ◽

Goo-Bo Jeong ◽

...

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Essential Role ◽

Regulatory Elements ◽

Intestinal Cells ◽

Human Leukemia ◽

Runt Domain ◽

C Elegans ◽

Intron Region

ABSTRACT The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an essential role in osteogenesis, and inactivation of one allele of Runx2 is responsible for the human disease cleidocranial dysplasia. To understand the role of run in C. elegans, we used transgenic run::GFP reporter constructs and a double-stranded RNA-mediated interference method. The expression of run was detected as early as the bean stage exclusively in the nuclei of seam hypodermal cells and lasted until the L3 stage. At the larval stage, expression of run was additionally detected in intestinal cells. The regulatory elements responsible for the postembryonic hypodermal seam cells and intestinal cells were separately located within a 7.2-kb-long intron region. This is the first report demonstrating that an intron region is essential for stage-specific and cell type-specific expression of a C. elegans gene. RNA interference analysis targeting the run gene resulted in an early larva-lethal phenotype, with apparent malformation of the hypodermis and intestine. These results suggest that run is involved in the development of a functional hypodermis and gut in C. elegans. The highly conserved role of the Runt domain transcription factor in gut development during evolution from nematodes to mammals is discussed.

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Targeted Disruption of the Mn1 Oncogene Results in Severe Defects in Development of Membranous Bones of the Cranial Skeleton

Molecular and Cellular Biology ◽

10.1128/mcb.25.10.4229-4236.2005 ◽

2005 ◽

Vol 25 (10) ◽

pp. 4229-4236 ◽

Cited By ~ 35

Author(s):

Magda A. Meester-Smoor ◽

Marcel Vermeij ◽

Marjolein J. L. van Helmond ◽

Anco C. Molijn ◽

Karel H. M. van Wely ◽

...

Keyword(s):

Transcription Factor ◽

Cleft Palate ◽

Myeloid Leukemia ◽

Tumor Formation ◽

Incomplete Penetrance ◽

Dna Binding Domain ◽

Wild Type ◽

Intramembranous Ossification ◽

Targeted Disruption

ABSTRACT Fusion of the MN1 gene to TEL (ETV6) results in myeloid leukemia. The fusion protein combines the transcription activating domain of MN1 and the DNA binding domain of TEL and is thought to act as a deranged transcription factor. In addition, disruption of the large first exon of the MN1 gene is thought to inactivate MN1 function in a meningioma. To further investigate the role of MN1 in cancer, we generated Mn1 knockout mice. Mn1 +/− animals were followed for 30 months, but they had no higher incidence of tumor formation than wild-type littermates. Mn1 null mice, however, were found to die at birth or shortly thereafter as the result of a cleft palate. Investigation of newborn or embryonic day 15.5 (E15.5) to E17.5 null mice revealed that the development of several bones in the skull was abnormal. The affected bones are almost exclusively formed by intramembranous ossification. They are either completely agenic at birth (alisphenoid and squamosal bones and vomer), hypoplastic, deformed (basisphenoid, pterygoid, and presphenoid), or substantially thinner (frontal, parietal, and interparietal bones). In heterozygous mice hypoplastic membranous bones and incomplete penetrance of the cleft palate were observed. We conclude that Mn1 is an important factor in development of membranous bones.

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Insulin-like peptides and the mTOR-TFEB pathway protect Caenorhabditis elegans hermaphrodites from mating-induced death

eLife ◽

10.7554/elife.46413 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Cheng Shi ◽

Lauren N Booth ◽

Coleen T Murphy

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Nuclear Localization ◽

Seminal Fluid ◽

Protective Role ◽

Successful Reproduction ◽

Insulin Antagonist ◽

Sperm Depletion

Lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males’ hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize.

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Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30

10.1101/2021.02.25.432801 ◽

2021 ◽

Author(s):

Benson Otarigho ◽

Alejandro Aballay

Keyword(s):

Nervous System ◽

Transcription Factor ◽

Caenorhabditis Elegans ◽

G Protein ◽

Neural Control ◽

Dependent Manner ◽

G Protein Coupled ◽

Y Receptors ◽

Neuropeptide Y Receptors

A body of evidence indicates that metazoan immune and aging pathways are largely interconnected, but the mechanisms involved in their homeostatic control remain unclear. In this study, we found that the PITX (paired like homeodomain) transcription factor UNC-30 controls the tradeoff between immunity and longevity from the nervous system in Caenorhabditis elegans. PITX/UNC-30 functional loss enhanced immunity in a GATA/ELT-2- and p38 MAPK/PMK-1-dependent manner and reduced longevity by activating the MXD/MDL-1 and PQM-1 pathways. The immune inhibitory and longevity stimulatory functions of PITX/UNC-30 required the sensory neuron ASG and a neurotransmitter signaling pathway controlled by NPR-1, which is a G protein-coupled receptor related to mammalian neuropeptide Y receptors. Our findings uncovered a suppressive role of GABAergic signaling in the neural control of a biological tradeoff where energy is allocated towards immunity at the expense of longevity.

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Identification of Caenorhabditis elegans Genes Required for Neuronal Differentiation and Migration

Genetics ◽

10.1093/genetics/148.1.151 ◽

1998 ◽

Vol 148 (1) ◽

pp. 151-165 ◽

Cited By ~ 2

Author(s):

Wayne C Forrester ◽

Elliot Perens ◽

Jennifer A Zallen ◽

Gian Garriga

Keyword(s):

Caenorhabditis Elegans ◽

Neuronal Differentiation ◽

Homeodomain Protein ◽

C Elegans ◽

Differentiation Marker ◽

And Migration ◽

Null Mutants ◽

Migrating Cells

Abstract To understand the mechanisms that guide migrating cells, we have been studying the embryonic migrations of the C. elegans canal-associated neurons (CANs). Here, we describe two screens used to identify genes involved in CAN migration. First, we screened for mutants that died as clear larvae (Clr) or had withered tails (Wit), phenotypes displayed by animals lacking normal CAN function. Second, we screened directly for mutants with missing or misplaced CANs. We isolated and characterized 30 mutants that defined 14 genes necessary for CAN migration. We found that one of the genes, ceh-10, specifies CAN fate. ceh-10 had been defined molecularly as encoding a homeodomain protein expressed in the CANs. Mutations that reduce ceh-10 function result in Wit animals with CANs that are partially defective in their migrations. Mutations that eliminate ceh-10 function result in Clr animals with CANs that fail to migrate or express CEH-23, a CAN differentiation marker. Null mutants also fail to express CEH-10, suggesting that CEH-10 regulates its own expression. Finally, we found that ceh-10 is necessary for the differentiation of AIY and RMED, two additional cells that express CEH-10.

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XBX-1 Encodes a Dynein Light Intermediate Chain Required for Retrograde Intraflagellar Transport and Cilia Assembly in Caenorhabditis elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e02-10-0677 ◽

2003 ◽

Vol 14 (5) ◽

pp. 2057-2070 ◽

Cited By ~ 84

Author(s):

Jenny C. Schafer ◽

Courtney J. Haycraft ◽

James H. Thomas ◽

Bradley K. Yoder ◽

Peter Swoboda

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Sensory Neurons ◽

Intraflagellar Transport ◽

Anterograde Transport ◽

Behavioral Abnormalities ◽

Genes Encoding ◽

Intermediate Chain

Intraflagellar transport (IFT) is a process required for flagella and cilia assembly that describes the dynein and kinesin mediated movement of particles along axonemes that consists of an A and a B complex, defects in which disrupt retrograde and anterograde transport, respectively. Herein, we describe a novel Caenorhabditis elegans gene, xbx-1, that is required for retrograde IFT and shares homology with a mammalian dynein light intermediate chain (D2LIC). xbx-1 expression in ciliated sensory neurons is regulated by the transcription factor DAF-19, as demonstrated previously for genes encoding IFT complex B proteins. XBX-1 localizes to the base of the cilia and undergoes anterograde and retrograde movement along the axoneme. Disruption of xbx-1 results in cilia defects and causes behavioral abnormalities observed in other cilia mutants. Analysis of cilia in xbx-1 mutants reveals that they are shortened and have a bulb like structure in which IFT proteins accumulate. The role of XBX-1 in IFT was further confirmed by analyzing the effect that other IFT mutations have on XBX-1 localization and movement. In contrast to other IFT proteins, retrograde XBX-1 movement was detected in complex A mutants. Our results suggest that the DLIC protein XBX-1 functions together with the CHE-3 dynein in retrograde IFT, downstream of the complex A proteins.

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