The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons

Development ◽  
1999 ◽  
Vol 126 (7) ◽  
pp. 1547-1562 ◽  
Author(s):  
O. Hobert ◽  
K. Tessmar ◽  
G. Ruvkun
Keyword(s):  
Epithelial Cells ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Acid Decarboxylase ◽  
Neural Function ◽  
C Elegans ◽  
Gaba Synthesis ◽  
And Function ◽  
Rate Limiting ◽  
Enteric Muscle

We describe here the functional analysis of the C. elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system. In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C. elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects.

Regulation of ectodermal and excretory function by the C. elegans POU homeobox gene ceh-6

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 779-790 ◽  
Author(s):  
T.R. Burglin ◽  
G. Ruvkun
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Null Mutant ◽  
Reporter Construct ◽  
Excretory Function ◽  
C Elegans ◽  
Gfp Reporter ◽  
Excretory Cell

Caenorhabditis elegans has three POU homeobox genes, unc-86, ceh-6 and ceh-18. ceh-6 is the ortholog of vertebrate Brn1, Brn2, SCIP/Oct6 and Brn4 and fly Cf1a/drifter/ventral veinless. Comparison of C. elegans and C. briggsae CEH-6 shows that it is highly conserved. C. elegans has only three POU homeobox genes, while Drosophila has five that fall into four families. Immunofluorescent detection of the CEH-6 protein reveals that it is expressed in particular head and ventral cord neurons, as well as in rectal epithelial cells, and in the excretory cell, which is required for osmoregulation. A deletion of the ceh-6 locus causes 80% embryonic lethality. During morphogenesis, embryos extrude cells in the rectal region of the tail or rupture, indicative of a defect in the rectal epithelial cells that express ceh-6. Those embryos that hatch are sick and develop vacuoles, a phenotype similar to that caused by laser ablation of the excretory cell. A GFP reporter construct expressed in the excretory cell reveals inappropriate canal structures in the ceh-6 null mutant. Members of the POU-III family are expressed in tissues involved in osmoregulation and secretion in a number of species. We propose that one evolutionary conserved function of the POU-III transcription factor class could be the regulation of genes that mediate secretion/osmoregulation.

VP16-activation of the C. elegans neural specification transcription factor UNC-86 suppresses mutations in downstream genes and causes defects in neural migration and axon outgrowth

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1159-1168 ◽  
Author(s):  
J.Y. Sze ◽  
Y. Liu ◽  
G. Ruvkun
Keyword(s):  
Transcription Factor ◽  
Homeobox Gene ◽  
Regulatory Sequences ◽  
General Strategy ◽  
Cell Fates ◽  
C Elegans ◽  
Expression Of Genes ◽  
Normal Expression ◽  
Neural Specification ◽  
And Function

The POU homeobox gene unc-86 specifies many neuroblast and neural fates in the developing C. elegans nervous system. Genes regulated by unc-86 are mostly unknown. Here we describe a genetic strategy for the identification of downstream pathways regulated by unc-86. We activate UNC-86 transcription activity by inserting the VP16 activation domain into an unc-86 genomic clone that bears all regulatory sequences necessary for normal expression in C. elegans. unc-86/VP16 complements unc-86 mutations in the specification of neuroblast and neural cell fates, but displays novel genetic activities: it can suppress non-null mutations in the downstream genes mec-3 and mec-7 that are necessary for mechanosensory neuron differentiation and function. These data suggest that UNC-86/VP16 increases the expression of mec-3 and mec-7 to compensate for the decreased activities of mutant MEC-3 or MEC-7 proteins. The suppression of mutations in downstream genes by an activated upstream transcription factor should be a general strategy for the identification of genes in transcriptional cascades. unc-86/VP16 also causes neural migration and pathfinding defects and novel behavioral defects. Thus, increased or unregulated expression of genes downstream of unc-86 can confer novel neural phenotypes suggestive of roles for unc-86-regulated genes in neural pathfinding and function. Genetic suppression of these unc-86/VP16 phenotypes may identify the unc-86 downstream genes that mediate these events in neurogenesis.

scholarly journals A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1951-1969 ◽  
Author(s):  
Zeynep Altun-Gultekin ◽  
Yoshiki Andachi ◽  
Ephraim L. Tsalik ◽  
David Pilgrim ◽  
Yuji Kohara ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
Homeobox Genes ◽  
Homeobox Gene ◽  
Homeodomain Proteins ◽  
Differentiation Markers ◽  
Regulatory Relationship ◽  
C Elegans ◽  
Regulatory Cascade ◽  
The Individual

The development of the nervous system requires the coordinated activity of a variety of regulatory factors that define the individual properties of specific neuronal subtypes. We report a regulatory cascade composed of three homeodomain proteins that act to define the properties of a specific interneuron class in the nematode C. elegans. We describe a set of differentiation markers characteristic for the AIY interneuron class and show that the ceh-10 paired-type and ttx-3 LIM-type homeobox genes function to regulate all known subtype-specific features of the AIY interneurons. In contrast, the acquisition of several pan-neuronal features is unaffected in ceh-10 and ttx-3 mutants, suggesting that the activity of these homeobox genes separates pan-neuronal from subtype-specific differentiation programs. The LIM homeobox gene ttx-3 appears to play a central role in regulation of AIY differentiation. Not only are all AIY subtype characteristics lost in ttx-3 mutants, but ectopic misexpression of ttx-3 is also sufficient to induce AIY-like features in a restricted set of neurons. One of the targets of ceh-10 and ttx-3 is a novel type of homeobox gene, ceh-23. We show that ceh-23 is not required for the initial adoption of AIY differentiation characteristics, but instead is required to maintain the expression of one defined AIY differentiation feature. Finally, we demonstrate that the regulatory relationship between ceh-10, ttx-3 and ceh-23 is only partially conserved in other neurons in the nervous system. Our findings illustrate the complexity of transcriptional regulation in the nervous system and provide an example for the intricate interdependence of transcription factor action.

A new Drosophila homeobox gene, bsh, is expressed in a subset of brain cells during embryogenesis

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 793-806 ◽  
Author(s):  
B. Jones ◽  
W. McGinnis
Keyword(s):  
Homeobox Genes ◽  
Homeobox Gene ◽  
Brain Morphology ◽  
Genetic Screens ◽  
Internal Structures ◽  
Drosophila Brain ◽  
And Function ◽  
The Brain

Homeobox genes have been shown to control the determination of positional, tissue and cellular identity during the development of the fruitfly Drosophila melanogaster. Because genes involved in the determination of internal structures derived from neural, mesodermal and endodermal tissues may have been overlooked in conventional genetic screens, we undertook the identification of new homeobox genes expressed in these internal tissues. Here we describe the characterization of one of these new Drosophila homeobox genes, called brain-specific-homeobox (bsh). In embryos, bsh is expressed exclusively in the brain. bsh protein accumulates in approximately 30 cells in each brain hemisphere. One of these bsh expressing cells is closely associated with the terminus of the larval visual nerve (Bolwig's nerve). While deletions of chromosomal interval containing the bsh gene show no dramatic changes in embryonic brain morphology, the expression pattern of the bsh gene suggests that it may play a highly specialized role in the determination and function of cell type in the Drosophila brain.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

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