Induction of identified mesodermal cells by CNS midline progenitors in Drosophila

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2681-2690 ◽  
Author(s):  
K. Luer ◽  
J. Urban ◽  
C. Klambt ◽  
G.M. Technau

The Drosophila ventral midline cells generate a discrete set of CNS lineages, required for proper patterning of the ventral ectoderm. Here we provide the first evidence that the CNS midline cells also exert inductive effects on the mesoderm. Mesodermal progenitors adjacent to the midline progenitor cells give rise to ventral somatic mucles and a pair of unique cells that come to lie dorsomedially on top of the ventral nerve cord, the so-called DM cells. Cell ablation as well as cell transplantation experiments indicate that formation of the DM cells is induced by midline progenitors in the early embryo. These results are corroborated by genetic analyses. Mutant single minded embryos lack the CNS midline as well as the DM cells. Embryos mutant for any of the spitz group genes, which primarily express defects in the midline glial cell lineages, show reduced formation of the DM cells. Conversely, directed overexpression of secreted SPITZ by some or all CNS midline cells leads to the formation of additional DM cells. Furthermore we show that DM cell development does not depend on the absolute concentration of a local inductor but appears to require a graded source of an inducing signal. Thus, the Drosophila CNS midline cells play a central inductive role in patterning the mesoderm as well as the underlying ectoderm.

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4949-4958 ◽  
Author(s):  
T.V. Menne ◽  
K. Luer ◽  
G.M. Technau ◽  
C. Klambt

Cells located at the midline of the developing central nervous system perform a number of conserved functions during the establishment of the lateral CNS. The midline cells of the Drosophila CNS were previously shown to be required for correct pattern formation in the ventral ectoderm and for the induction of specific mesodermal cells. Here we investigated whether the midline cells are required for the correct development of lateral CNS cells as well. Embryos that lack midline cells through genetic ablation show a 15% reduction in the number of cortical CNS cells. A similar thinning of the ventral nerve cord can be observed following mechanical ablation of the midline cells. We have identified a number of specific neuronal and glial cell markers that are reduced in CNS midline-less embryos (in single-minded embryos, in early heat-shocked Notch(ts1) embryos or in embryos where we mechanically ablated the midline cells). Genetic data suggest that both neuronal and glial midline cell lineages are required for differentiation of lateral CNS cells. We could rescue the lateral CNS phenotype of single-minded mutant embryos by transplantation of midline cells as well as by homotopic expression of single-minded, the master gene for midline development. Furthermore, ectopic midline cells are able to induce enhanced expression of some lateral CNS cell markers. We thus conclude that the CNS midline plays an important role in the differentiation or maintenance of the lateral CNS cortex.


Development ◽  
1998 ◽  
Vol 125 (9) ◽  
pp. 1599-1608 ◽  
Author(s):  
M.P. Ward ◽  
J.T. Mosher ◽  
S.T. Crews

The Drosophila Single-minded and Tango basic-helix-loop-helix-PAS protein heterodimer controls transcription and embryonic development of the CNS midline cells, while the Trachealess and Tango heterodimer controls tracheal cell and salivary duct transcription and development. Expression of both single-minded and trachealess is highly restricted to their respective cell lineages, however tango is broadly expressed. The developmental control of subcellular localization of these proteins is investigated because of their similarity to the mammalian basic-helix-loop-helix-PAS Aromatic hydrocarbon receptor whose nuclear localization is dependent on ligand binding. Confocal imaging of Single-minded and Trachealess protein localization indicate that they accumulate in cell nuclei when initially synthesized in their respective cell lineages and remain nuclear throughout embryogenesis. Ectopic expression experiments show that Single-minded and Trachealess are localized to nuclei in cells throughout the ectoderm and mesoderm, indicating that nuclear accumulation is not regulated in a cell-specific fashion and unlikely to be ligand dependent. In contrast, nuclear localization of Tango is developmentally regulated; it is localized to the cytoplasm in most cells except the CNS midline, salivary duct, and tracheal cells where it accumulates in nuclei. Genetic and ectopic expression experiments indicate that Tango nuclear localization is dependent on the presence of a basic-helix-loop-helix-PAS protein such as Single-minded or Trachealess. Conversely, Drosophila cell culture experiments show that Single-minded and Trachealess nuclear localization is dependent on Tango since they are cytoplasmic in the absence of Tango. These results suggest a model in which Single-minded and Trachealess dimerize with Tango in the cytoplasm of the CNS midline cells and trachea, respectively, and the dimeric complex accumulates in nuclei in a ligand-independent mode and regulates lineage-specific transcription. The lineage-specific action of Single-minded and Trachealess derives from transcriptional activation of their genes in their respective lineages, not from extracellular signaling.


2002 ◽  
Vol 22 (12) ◽  
pp. 4147-4157 ◽  
Author(s):  
Eleni Goshu ◽  
Hui Jin ◽  
Rachel Fasnacht ◽  
Mike Sepenski ◽  
Jacques L. Michaud ◽  
...  

ABSTRACT The mouse genome contains two Sim genes, Sim1 and Sim2. They are presumed to be important for central nervous system (CNS) development because they are homologous to the Drosophila single-minded (sim) gene, mutations in which cause a complete loss of CNS midline cells. In the mammalian CNS, Sim2 and Sim1 are coexpressed in the paraventricular nucleus (PVN). While Sim1 is essential for the development of the PVN (J. L. Michaud, T. Rosenquist, N. R. May, and C.-M. Fan, Genes Dev. 12:3264-3275, 1998), we report here that Sim2 mutant has a normal PVN. Analyses of the Sim1 and Sim2 compound mutants did not reveal obvious genetic interaction between them in PVN histogenesis. However, Sim2 mutant mice die within 3 days of birth due to lung atelectasis and breathing failure. We attribute the diminished efficacy of lung inflation to the compromised structural components surrounding the pleural cavity, which include rib protrusions, abnormal intercostal muscle attachments, diaphragm hypoplasia, and pleural mesothelium tearing. Although each of these structures is minimally affected, we propose that their combined effects lead to the mechanical failure of lung inflation and death. Sim2 mutants also develop congenital scoliosis, reflected by the unequal sizes of the left and right vertebrae and ribs. The temporal and spatial expression patterns of Sim2 in these skeletal elements suggest that Sim2 regulates their growth and/or integrity.


2021 ◽  
Author(s):  
Yao Lulu Xing ◽  
Bernard H.A. Chuang ◽  
Jasmine Poh ◽  
Kaveh Moradi ◽  
Stanislaw Mitew ◽  
...  

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent central nervous system have been limited by methodological challenges resulting in only partial and transient OPC depletion. We have developed a novel pharmacogenetic model of conditional OPC ablation, resulting in the elimination of 99.7% of all OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting of OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRα-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRα+/NG2+ cells with the capacity to migrate and proliferate extensively throughout the dorsal anterior forebrain. Further application of this novel approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease.


Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 65-73 ◽  
Author(s):  
Robert K. Ho

The early lineages of the zebrafish are indeterminate and a single cell labeled before the late blastula period will contribute progeny to a variety of tissues. Therefore, early cell lineages in the zebrafish do not establish future cell fates and early blastomeres must necessarily remain pluripotent. Eventually, after a period of random cell mixing, individual cells do become tissue restricted according to their later position within the blastoderm. The elucidation of a fate map for the zebrafish gastrula (Kimmel et al., 1990), has made it possible to study the processes by which cellular identity is conferred and maintained in the zebrafish. In this chapter, I describe single cell transplantation experiments designed to test for the irreversible restriction or ‘commitment’ of embryonic blastomeres in the zebrafish embryo. These experiments support the hypothesis that cell fate in the vertebrate embryo is determined by cell position. Work on the spadetail mutation will also be reviewed; this mutation causes a subset of mesodermal precursors to mismigrate during gastrulation thereby leading to a change in their eventual cell identity.


Development ◽  
2001 ◽  
Vol 128 (17) ◽  
pp. 3243-3251 ◽  
Author(s):  
Christian Berger ◽  
Joachim Urban ◽  
Gerhard M. Technau

One of the initial steps of neurogenesis in the Drosophila embryo is the delamination of a stereotype set of neural progenitor cells (neuroblasts) from the neuroectoderm. The time window of neuroblast segregation has been divided into five successive waves (S1-S5) in which subsets of neuroblasts with specific identities are formed. To test when identity specification of the various neuroblasts takes place and whether extrinsic signals are involved, we have performed heterochronic transplantation experiments. Single neuroectodermal cells from stage 10 donor embryos (after S2) were transplanted into the neuroectoderm of host embryos at stage 7 (before S1) and vice versa. The fate of these cells was uncovered by their lineages at stage 16/17. Transplanted cells adjusted their fate to the new temporal situation. Late neuroectodermal cells were able to take over the fate of early (S1/S2) neuroblasts. The early neuroectodermal cells preferentially generated late (S4/S5) neuroblasts, despite their reduced time of exposure to the neuroectoderm. Furthermore, neuroblast fates are independent from divisions of neuroectodermal progenitor cells. We conclude from these experiments that neuroblast specification occurs sequentially under the control of non-cell-autonomous and stage-specific inductive signals that act in the neuroectoderm.


2006 ◽  
Vol 294 (2) ◽  
pp. 509-524 ◽  
Author(s):  
Scott R. Wheeler ◽  
Joseph B. Kearney ◽  
Amaris R. Guardiola ◽  
Stephen T. Crews

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