Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin

Blood ◽  
2021 ◽  
Author(s):  
Christopher Michael Hoover ◽  
Yuji Kondo ◽  
Bojing Shao ◽  
Michael McDaniel ◽  
Robert Lee ◽  
...  

During early embryonic development in mammals, including humans and mice, megakaryocytes first originate from primitive hematopoiesis in the yolk sac. These embryonic megakaryocytes (eMk) circulate in the vasculature with unclear function. Here we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on megakaryocytes/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to lower diencephalon in mutant mouse embryos than wild-type littermates prior to hemorrhage. We found that PDPN counteracted the collagen I-induced secretion of angiopoietin-1 from fetal megakaryocytes, which coincided with enhanced TIE2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

2000 ◽  
Vol 98 (1-2) ◽  
pp. 175-178 ◽  
Author(s):  
Cornelia Leimeister ◽  
Nina Schumacher ◽  
Christian Steidl ◽  
Manfred Gessler

2017 ◽  
Vol 231 (4) ◽  
pp. 600-614 ◽  
Author(s):  
Stefan H. Geyer ◽  
Lukas F. Reissig ◽  
Markus Hüsemann ◽  
Cordula Höfle ◽  
Robert Wilson ◽  
...  

2003 ◽  
Vol 264 (2) ◽  
pp. 537-549 ◽  
Author(s):  
Giovanna L Liguori ◽  
Diego Echevarría ◽  
Raffaele Improta ◽  
Massimo Signore ◽  
Eileen Adamson ◽  
...  

1985 ◽  
Vol 79 (1) ◽  
pp. 305-315
Author(s):  
S. Anderson ◽  
D.A. Ede

Pupoid foetus (pf/pf) is a recessive lethal mutation of the mouse causing epidermal hypertrophy and disorganization of peripheral sensory nerves and mesoderm. The comparative behaviour of epidermal cells from normal and pupoid foetus mutant mouse embryos was studied in vitro. Epidermal explants from the snout region of 12.5- to 13-day embryos were grown in culture for periods of up to 2 weeks. Cultures from both phenotypes were filmed using time-lapse cinemicrography for up to 3 days following explantation. Paths of individual cells were traced as they migrated from the explant, and their rate of locomotion and directional persistence were calculated. Differences in these parameters between the two phenotypes were tested statistically. The overall morphology of the cultures, and the tendency of the cells to detach from the periphery of the cell mass were also compared. The results show that, between 25 and 60 h after explantation, epidermal cells from pupoid foetus embryos move consistently more slowly than normal cells, and follow a more erratic path. This situation is reversed, however, between 16 and 25 h. This suggests that the pf mutation causes an alteration in epidermal cells that affects their locomotion, and which is maintained for a minimum of 3 days in the absence of other influencing factors.


Development ◽  
1978 ◽  
Vol 45 (1) ◽  
pp. 189-202
Author(s):  
O. P. Flint ◽  
D. A. Ede ◽  
O. K. Wilby ◽  
J. Proctor

A regulation is shown for size and number of serially repeated axial structures, the somites, in a mammalian embryo. The mammalian embryo is normally inaccessible to operation at post-implantation stages. This problem is resolved by the quantitative analysis of somite size, number and development in a recessive mutant of the mouse, amputated, whose axial length is greatly reduced. The effect of the gene simulates an experiment ablating part of the embryonic tissue available for somitic segmentation. Regulation occurs at the time when the somite is first formed, by control of the quantity of cells included in each new somite. A model is devised for the control of somitic segmentation which explains most of the features observed and which can be simulated on a computer.


BMC Genomics ◽  
2008 ◽  
Vol 9 (1) ◽  
pp. 511 ◽  
Author(s):  
Owen J Tamplin ◽  
Doris Kinzel ◽  
Brian J Cox ◽  
Christine E Bell ◽  
Janet Rossant ◽  
...  

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