Genetic mosaic analysis in the nervous system

2004 ◽  
Vol 14 (5) ◽  
pp. 647-653 ◽  
Author(s):  
Christopher T Zugates ◽  
Tzumin Lee
Keyword(s):  
Nervous System ◽  
Genetic Mosaic ◽  
Mosaic Analysis

The expression of TGFβ signal transducers in the hypodermis regulates body size inC. elegans

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 4989-4998 ◽  
Author(s):  
Jianjun Wang ◽  
Rafal Tokarz ◽  
Cathy Savage-Dunn
Keyword(s):  
Nervous System ◽  
Body Size ◽  
Protein Accumulation ◽  
Type I ◽  
Loss Of Function ◽  
Signal Transducers ◽  
C Elegans ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Necessary And Sufficient

In C. elegans, a TGFβ-related signaling pathway regulates body size. Loss of function of the signaling ligand (dbl-1),receptors (daf-4 and sma-6) or Smads (sma-2, sma-3and sma-4) results in viable, but smaller animals because of a reduction in postembryonic growth. We have investigated the tissue specificity of this pathway in body size regulation. We show that different tissues are reduced in size by different proportions, with hypodermal blast cell size most closely proportional to body size. We show that SMA-3 Smad is expressed in pharynx, intestine and hypodermis, as has been previously reported for the type I receptor SMA-6. Furthermore, we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity. Interestingly, SMA-3 protein accumulation was found to be negatively regulated by the level of Sma/Mab pathway activity. Using genetic mosaic analysis and directed expression of SMA-3, we find that SMA-3 activity in the hypodermis is necessary and sufficient for normal body size. Asdbl-1 is expressed primarily in the nervous system, these results suggest a model in which postembryonic growth of hypodermal cells is regulated by TGFβ-related signaling from the nervous system to the hypodermis.

scholarly journals A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

2020 ◽  
Author(s):  
Ximena Contreras ◽  
Amarbayasgalan Davaatseren ◽  
Nicole Amberg ◽  
Andi H. Hansen ◽  
Johanna Sonntag ◽  
...  
Keyword(s):  
Single Cell ◽  
Genetic Mosaic ◽  
Genome Wide ◽  
A Genome ◽  
Mosaic Analysis

Caenorhabditis elegans lin-25: cellular focus, protein expression and requirement for sur-2 during induction of vulval fates

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4809-4819 ◽  
Author(s):  
L. Nilsson ◽  
X. Li ◽  
T. Tiensuu ◽  
R. Auty ◽  
I. Greenwald ◽  
...  
Keyword(s):  
Protein Expression ◽  
Map Kinase ◽  
Signal Transduction Pathway ◽  
Precursor Cells ◽  
C Elegans ◽  
Novel Proteins ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Map Kinase Pathway ◽  
Cell Fusions

Induction of vulval fates in the C. elegans hermaphrodite is mediated by a signal transduction pathway involving Ras and MAP kinase. Previous genetic analysis has suggested that two potential targets of this pathway in the vulva precursor cells are two novel proteins, LIN-25 and SUR-2. In this report, we describe further studies of lin-25. The results of a genetic mosaic analysis together with those of experiments in which lin-25 was expressed under the control of an heterologous promoter suggest that the major focus of lin-25 during vulva induction is the vulva precursor cells themselves. We have generated antisera to LIN-25 and used these to analyse the pattern of protein expression. LIN-25 is present in all six precursor cells prior to and during vulva induction but later becomes restricted to cells of the vulval lineages. Mutations in genes in the Ras/MAP kinase pathway do not affect the pattern of expression but the accumulation of LIN-25 is reduced in the absence of sur-2. Overexpression of LIN-25 does not rescue sur-2 mutant defects suggesting that LIN-25 and SUR-2 may function together. LIN-25 is also expressed in the lateral hypodermis. Overexpression of LIN-25 disrupts lateral hypodermal cell fusion, suggesting that lin-25 may play a role in regulating cell fusions in C. elegans.

scholarly journals Clonal Analysis of Gliogenesis in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2662
Author(s):  
Xuying Zhang ◽  
Christine V. Mennicke ◽  
Guanxi Xiao ◽  
Robert Beattie ◽  
Mansoor A. Haider ◽  
...  
Keyword(s):  
Nervous System ◽  
Epidermal Growth Factor Receptor ◽  
Cerebral Cortex ◽  
Biological Significance ◽  
Growth Factor Receptor ◽  
Clonal Analysis ◽  
Proliferation Capacity ◽  
Mosaic Analysis ◽  
Epidermal Growth ◽  
Genetic Deletion

Development of the nervous system undergoes important transitions, including one from neurogenesis to gliogenesis which occurs late during embryonic gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic Analysis with Double Markers (MADM) with quantitative and computational methods. Results reveal that developmental gliogenesis in the cerebral cortex occurs in a fraction of earlier neurogenic clones, accelerating around E16.5, and giving rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices. A broad range in the proliferation capacity, symmetry of clones, and competitive advantage of MADM cells was evident in clones that contained one cellular lineage with double dosage of Egfr relative to their environment, while their sibling Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia in MADM clones balance out regardless of significant alterations in clonal symmetries. The variability in glial clones shows stochastic patterns that we define mathematically, which are different from the deterministic patterns in neuronal clones. This study sets a foundation for studying the biological significance of stochastic and deterministic clonal principles underlying tissue development, and identifying mechanisms that differentiate between neurogenesis and gliogenesis.

scholarly journals Mosaic Analysis of the Liguleless3 Mutant Phenotype in Maize by Coordinate Suppression of Mutator-insertion Alleles

Genetics ◽  
1996 ◽  
Vol 143 (1) ◽  
pp. 489-503 ◽  
Author(s):  
John E Fowler ◽  
Gary J Muehlbauer ◽  
Michael Freeling
Keyword(s):  
Regional Identity ◽  
Transverse Dimension ◽  
Mutant Phenotype ◽  
Specific Cell ◽  
Wild Type ◽  
Cell Fates ◽  
Active Line ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Cell Autonomy

Abstract Ligubless3-O (Lg3-O) transforms the leaf blade, auricle and ligule into sheath around the midrib region. We conducted a genetic mosaic analysis of the Lg3 phenotype to determine the site of Lg3 gene action. Combining the Mutator (Mu) suppressible Lg3-Or211 and al-mum2 alleles in a Mu-active background generated a stock wherein somatic loss of Mu activity resulted in anthocyanin-marked clonal sectors expressing Lg3 in the leaf. Lg3-Or211 plants appear wild type in a Mu-active line, but Mu-inactive plants express a severe Lg3 phenotype. We observed four sector classes: wild type, sheath-like with ligule displacement, sheath-like with ectopic ligule, and auricle-like. The mutation does not cause transformation to a specific cell or regional identity. Lg3-Or211 activity in the mesophyll alters wild-type epidermal cell fates; activity in epidermis seems funtionless. Lg3 mutant activity has a nonautonomous, cell-layer-specific function in the transverse dimension. In the lateral dimension, sectors of Lg3 mutant phenotype can exhibit either cell-autonomous or nonautonomous effects. Our work demonstrates that mosaic analysis by coordinate suppression of Mu-induced alleles is useful for analyzing the cell autonomy of genetically defined functions.

scholarly journals A New Marker for Mosaic Analysis in Caenorhabditis elegans Indicates a Fusion Between hyp6 and hyp7, Two Major Components of the Hypodermis

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1323-1334 ◽  
Author(s):  
John Yochem ◽  
Trent Gu ◽  
Min Han
Keyword(s):  
Caenorhabditis Elegans ◽  
Nuclear Localization Signal ◽  
Fluorescent Protein ◽  
Normal Growth ◽  
Immunofluorescent Staining ◽  
Nematode Caenorhabditis Elegans ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Localization Signal ◽  
Green Fluorescent

Abstract A fusion of the sur-5 protein to the green fluorescent protein containing a nuclear localization signal is demonstrated as a marker for genetic mosaic analysis in the nematode Caenorhabditis elegans. Because of an extensive accumulation of bright fluorescence in many nuclei, normal growth plates, each containing hundreds of worms, can be rapidly screened with a dissecting microscope for rare mosaic individuals. As the marker can also be used to detect transgenic worms, the construction of strains for mosaic analyses can be minimized. In the course of examining rare mosaic animals, an unexpected pattern of fluorescence was noticed for hyp6, a syncytial component of the hypodermis, which indicated that the marker may serve as a means of assessing cellular fusions during development. Immunofluorescent staining of adherens junctions confirmed a postembryonic fusion of hyp6 with hyp7, the major syncytium of the hypodermis.

scholarly journals The mup-4 Locus in Caenorhabditis elegans Is Essential for Hypodermal Integrity, Organismal Morphogenesis and Embryonic Body Wall Muscle Position

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 165-183
Author(s):  
Beth K Gatewood ◽  
Elizabeth A Bucher
Keyword(s):  
Caenorhabditis Elegans ◽  
Muscle Cell ◽  
Body Shape ◽  
Body Wall ◽  
Body Wall Muscle ◽  
Successful Completion ◽  
The Third ◽  
Genetic Mosaic ◽  
Cell Position ◽  
Mosaic Analysis

mup-4 is a member of a set of genes essential for correct embryonic body wall muscle cell positions in Caenorhabditis elegans. The mup-4 phenotype is variably expressed and three discrete arrest phenotypes arise during the phase of embryonic development when the worm elongates from a ball of cells to its worm shape (organismal morphogenesis). Mutants representing two of the phenotypic classes arrest without successful completion of elongation. Mutants of the third phenotypic class arrest after completion of elongation. Mutants that arrest after elongation display profound dorsal and ventral body wall muscle cell position abnormalities and a characteristic kinked body shape (the Mup phenotype) dueto the muscle cell position abnormalities. Significantly, genetic mosaic analysis of mup-4 mutants demonstrates that mup-4 gene function is essential in the AB lineage, which generates most of the hypodermis (epidermis), a tissue with which muscle interacts. Consistent with the genetic mosaic data, phenotypic characterizations reveal that mutants have defects in hypodermal integrity and morphology. Our analyses support the conclusion that mup-4 is essential for hypodermal function and that this function is necessary for organismal morphogenesis and for the maintenance of body wall muscle position.

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