scholarly journals Developmental Characterization of Zswim5 Expression in the Progenitor Domains and Tangential Migration Pathways of Cortical Interneurons in the Mouse Forebrain

2019 ◽  
Author(s):  
Chuan-Chie Chang ◽  
Hsiao-Ying Kuo ◽  
Shih-Yun Chen ◽  
Kuan-Ming Lu ◽  
Weng Lam Fong ◽  
...  
Keyword(s):  
Cell Fate ◽  
Expression Pattern ◽  
Ganglionic Eminence ◽  
Double Labeling ◽  
Tangential Migration ◽  
Cortical Interneurons ◽  
Low Levels ◽  
Migration Pathways

ABSTRACTGABAergic interneurons play an essential role in modulating cortical networks. The progenitor domains of cortical interneurons are localized in developing ventral forebrain, including the medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE), preoptic area (POA) and preoptic hypothalamic border domain (POH). Here, we characterized the expression pattern of Zswim5, an MGE-enriched gene in the mouse forebrain. At E11.5 to E13.5, prominent Zswim5 expression was detected in the subventricular zone (SVZ) of MGE, CGE, POA and POH of ventral telencephalon in which progenitors of cortical interneurons resided. At E15.5 and E17.5, Zswim5 remained detectable in the SVZ of pallidal primordium (MGE). Zswim5 mRNA was markedly decreased after birth and was absent in the adult forebrain. Interestingly, Zswim5 expression pattern resembled the tangential migration pathways of cortical interneurons. Zswim5-positive cells in the MGE appeared to migrate from the MGE through the SVZ of LGE to overlying neocortex. Indeed, Zswim5 was co-localized with Nkx2.1 and Lhx6, markers of progenitos and migratory cortical interneurons. Double labeling showed that Mash1/Ascl1-positive cells did not express Zswim5. Zswim5 expressing cells showed none or at most low levels of Ki67 but co-expressed Tuj1 in the SVZ of MGE. These results suggest that Zswim5 is immediately upregulated as progenitors exiting cell cycle to become postmitotic. Given that recent studies have elucidated that the cell fate of cortical interneurons is determined shortly after postmitotic, the timing of Zswim5 expression in early postmitotic cortical interneurons suggests a potential role of Zswim5 in regulation of neurogenesis and tangential migration of cortical interneurons.

scholarly journals Developmental characterization of Zswim5 expression in the progenitor domains and tangential migration pathways of cortical interneurons in the mouse forebrain

2020 ◽  
Vol 528 (14) ◽  
pp. 2404-2419
Author(s):  
Chuan‐Chie Chang ◽  
Hsiao‐Ying Kuo ◽  
Shih‐Yun Chen ◽  
Wan‐Ting Lin ◽  
Kuan‐Ming Lu ◽  
...  
Keyword(s):  
Tangential Migration ◽  
Cortical Interneurons ◽  
Migration Pathways

Genes necessary for C. elegans cell and growth cone migrations

Development ◽  
1997 ◽  
Vol 124 (9) ◽  
pp. 1831-1843 ◽  
Author(s):  
W.C. Forrester ◽  
G. Garriga
Keyword(s):  
Cell Fate ◽  
Single Gene ◽  
Growth Cones ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
C Elegans ◽  
Final Destination ◽  
Multiple Cell

The migrations of cells and growth cones contribute to form and pattern during metazoan development. To study the mechanisms that regulate cell motility, we have screened for C. elegans mutants defective in the posteriorly directed migrations of the canal-associated neurons (CANs). Here we describe 14 genes necessary for CAN cell migration. Our characterization of the mutants has led to three conclusions. First, the mutations define three gene classes: genes necessary for cell fate specification, genes necessary for multiple cell migrations and a single gene necessary for final positioning of migrating cells. Second, cell interactions between the CAN and HSN, a neuron that migrates anteriorly to a position adjacent to the CAN, control the final destination of the HSN cell body. Third, C. elegans larval development requires the CANs. In the absence of CAN function, larvae arrest development, with excess fluid accumulating in their pseudocoeloms. This phenotype may reflect a role of the CANs in osmoregulation.

scholarly journals The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche

2015 ◽  
Vol 112 (29) ◽  
pp. 9052-9057 ◽  
Author(s):  
Billel Benmimoun ◽  
Cédric Polesello ◽  
Marc Haenlin ◽  
Lucas Waltzer
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Cell Fate ◽  
Hematopoietic Organ ◽  
Intrinsic Factors ◽  
Genetic Ablation ◽  
Systemic Signaling ◽  
Low Levels ◽  
Progenitor Maintenance

The maintenance of stem or progenitor cell fate relies on intrinsic factors as well as local cues from the cellular microenvironment and systemic signaling. In the lymph gland, an hematopoietic organ in Drosophila larva, a group of cells called the Posterior Signaling Centre (PSC), whose specification depends on the EBF transcription factor Collier (Col) and the HOX factor Antennapedia (Antp), has been proposed to form a niche required to maintain the pool of hematopoietic progenitors (prohemocytes). In contrast with this model, we show here that genetic ablation of the PSC does not cause an increase in blood cell differentiation or a loss of blood cell progenitors. Furthermore, although both col and Antp mutant larvae are devoid of PSC, the massive prohemocyte differentiation observed in col mutant is not phenocopied in Antp mutant. Interestingly, beside its expression in the PSC, Col is also expressed at low levels in prohemocytes and we show that this expression persists in PSC-ablated and Antp mutant larvae. Moreover, targeted knockdown and rescue experiments indicate that Col expression is required in the prohemocytes to prevent their differentiation. Together, our findings show that the PSC is dispensable for blood cell progenitor maintenance and reveal the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate.

scholarly journals The conserved ASCL1/MASH-1 ortholog HLH-3 specifies sex-specific ventral cord motor neuron fate in C. elegans

2020 ◽  
Author(s):  
Lillian M. Perez ◽  
Aixa Alfonso
Keyword(s):  
Motor Neuron ◽  
Cell Fate ◽  
Motor Neurons ◽  
Bhlh Protein ◽  
Differentiation Markers ◽  
C Elegans ◽  
Ventral Cord ◽  
Neural Specification

ABSTRACTNeural specification can be regulated by one or many transcription factors. Here we identify a novel role for one conserved proneural factor, the bHLH protein HLH-3, implicated in the specification of sex-specific ventral cord motor neurons in C. elegans. In the process of characterizing the role of hlh-3 in neural specification, we document that differentiation of the ventral cord type C neurons, VCs, within their motor neuron class, is dynamic in time and space. Expression of VC class-specific and subclass-specific identity genes is distinct through development and dependent on where they are along the A-P axis (and their position in proximity to the vulva). Our characterization of the expression of VC class and VC subclass-specific differentiation markers in the absence of hlh-3 function reveals that VC fate specification, differentiation, and morphology requires hlh-3 function. Finally, we conclude that hlh-3 cell-autonomously specifies VC cell fate.

Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1960-1967 ◽  
Author(s):  
Francis N. Karanu ◽  
Barbara Murdoch ◽  
Tomoyuki Miyabayashi ◽  
Mitsuhara Ohno ◽  
Masahide Koremoto ◽  
...  
Keyword(s):  
Cell Fate ◽  
Hematopoietic Cells ◽  
Functional Roles ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Deficient Mice

Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.

scholarly journals The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration

2019 ◽  
Vol 29 (12) ◽  
pp. 5116-5130 ◽  
Author(s):  
Jada Bittle ◽  
Edenia C Menezes ◽  
Michael L McCormick ◽  
Douglas R Spitz ◽  
Michael Dailey ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Restraint Stress ◽  
Time Lapse ◽  
Ganglionic Eminence ◽  
Cortical Interneuron ◽  
Redox Biology ◽  
Tangential Migration ◽  
Increased Risk ◽  
Induced Changes

Abstract Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and antioxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GAD67GFP+ interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence (GE), the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized DHE oxidation levels in GE and ameliorated the migration delay caused by prenatal stress. Through convergent redox manipula-tions, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.

scholarly journals Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes

2004 ◽  
Vol 200 (10) ◽  
pp. 1231-1241 ◽  
Author(s):  
Chunfeng Qu ◽  
Emmerson W. Edwards ◽  
Frank Tacke ◽  
Véronique Angeli ◽  
Jaime Llodrá ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Chemokine Receptors ◽  
Human Monocyte ◽  
Monocyte Subsets ◽  
Migration Pathways

Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX3CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX3CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1int monocyte population, and the number of latex+ DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1int monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1int monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.

Hedgehog Signaling in the Drosophila Eye and Head: An Analysis of the Effects of Differentpatched Trans-heterozygotes

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 1915-1928
Author(s):  
Chloe Thomas ◽  
Philip W Ingham
Keyword(s):  
Cell Fate ◽  
Hedgehog Signaling ◽  
Missense Mutations ◽  
Wild Type ◽  
Eye Size ◽  
C Terminus ◽  
Opposing Effects ◽  
Antennal Disc

AbstractCharacterization of different alleles of the Hedgehog receptor patched (ptc) indicates that they can be grouped into several classes. Most mutations result in complete loss of Ptc function. However, missense mutations located within the putative sterol-sensing domain (SSD) or C terminus of ptc encode antimorphic proteins that are unable to repress Smo activity and inhibit wild-type Ptc from doing so, but retain the ability to bind and sequester Hh. Analysis of the eye and head phenotypes of Drosophila melanogaster in various ptc/ptctuf1 heteroallelic combinations shows that these two classes of ptc allele can be easily distinguished by their eye phenotype, but not by their head phenotype. Adult eye size is inversely correlated with head vertex size, suggesting an alteration of cell fate within the eye-antennal disc. A balance between excess cell division and cell death in the mutant eye discs may also contribute to final eye size. In addition, contrary to results reported recently, the role of Hh signaling in the Drosophila head vertex appears to be primarily in patterning rather than in proliferation, with Ptc and Smo having opposing effects on formation of medial structures.

scholarly journals Hsp90 Is Required for Pheromone Signaling in Yeast

1998 ◽  
Vol 9 (11) ◽  
pp. 3071-3083 ◽  
Author(s):  
Jean-François Louvion ◽  
Toufik Abbas-Terki ◽  
Didier Picard
Keyword(s):  
Budding Yeast ◽  
Heat Shock Protein 90 ◽  
Wild Type ◽  
Pheromone Signaling ◽  
Endogenous Substrate ◽  
Low Levels ◽  
Biochemical Analyses ◽  
Map Kinase Pathways

The heat-shock protein 90 (Hsp90) is a cytosolic molecular chaperone that is highly abundant even at normal temperature. Specific functions for Hsp90 have been proposed based on the characterization of its interactions with certain transcription factors and kinases including Raf in vertebrates and flies. We therefore decided to address the role of Hsp90 for MAP kinase pathways in the budding yeast, an organism amenable to both genetic and biochemical analyses. We found that both basal and induced activities of the pheromone-signaling pathway depend on Hsp90. Signaling is defective in strains expressing low levels or point mutants of yeast Hsp90 (Hsp82), or human Hsp90β instead of the wild-type protein. Ste11, a yeast equivalent of Raf, forms complexes with wild-type Hsp90 and depends on Hsp90 function for accumulation. For budding yeast, Ste11 represents the first identified endogenous “substrate” of Hsp90. Moreover, Hsp90 functions in steroid receptor and pheromone signaling can be genetically separated as the Hsp82 point mutant T525I and the human Hsp90β are specifically defective for the former and the latter, respectively. These findings further corroborate the view that molecular chaperones must also be considered as transient or stable components of signal transduction pathways.

Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus

1986 ◽  
Vol 32 (6) ◽  
pp. 465-472 ◽  
Author(s):  
Dale Brown ◽  
Michael J. M. Hitchcock ◽  
Edward Katz
Keyword(s):  
Molecular Weight ◽  
Molecular Size ◽  
Purification And Characterization ◽  
Streptomyces Species ◽  
Specialized Function ◽  
Low Levels ◽  
Temperature Optima ◽  
Molecular Weight Form

Two forms of kynurenine formamidase (EC 3.5.1.9; aryl-formylamine amidohydrolase) are present in extracts of Streptomyces parvulus. The higher molecular weight enzyme (Mr = 42 000), kynurenine formamidase I, appears to be constitutive and is present at relatively constant but low levels in antibiotic producing and nonproducing cultures, whereas the synthesis of the lower molecular weight form (Mr = 25 000), kynurenine formamidase II, is initiated just prior to the onset of actinomycin formation. It is postulated (i) that kynurenine formamidase II catalyzes the second step in the pathway from tryptophan → actinocin, and (ii) that it is regulated specifically for the specialized function of actinomycin biosynthesis. The role of kynurenine formamidase I is unknown. Formamidase I and II activities were purified from extracts of S. parvulus and kinetic parameters of the two enzymes were determined. Although some of the properties of the two enzymes are quite similar (substrate specificities, Km values), some striking differences were noted (pH and temperature optima, molecular size, chromatographic properties, sensitivity to certain ions and chemicals). Mutant studies suggest that expression of the gene(s) coding for formamidase II activity play an essential role in regulating the formation of actinocin and, hence, antibiotic synthesis. Kynurenine formamidase activity was also found in a representative number of Streptomyces species and related organisms suggesting that the enzyme may function in the degradative metabolism of tryptophan by certain actinomycetes in nature.

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