scholarly journals Identifying Key Genetic Regions for Cell Sheet Morphogenesis on Chromosome 2L Using a Drosophila Deficiency Screen in Dorsal Closure

2020 ◽  
Vol 10 (11) ◽  
pp. 4249-4269
Author(s):  
Stephanie M. Fogerson ◽  
Richard D. Mortensen ◽  
Regan P. Moore ◽  
Hellen Y. Chiou ◽  
Neel K. Prabhu ◽  
...  

Cell sheet morphogenesis is essential for metazoan development and homeostasis of animal form – it contributes to developmental milestones including gastrulation, neural tube closure, heart and palate formation and to tissue maintenance during wound healing. Dorsal closure, a well-characterized stage in Drosophila embryogenesis and a model for cell sheet morphogenesis, is a remarkably robust process during which coordination of conserved gene expression patterns and signaling cascades regulate the cellular shape changes and movements. New ‘dorsal closure genes’ continue to be discovered due to advances in imaging and genetics. Here, we extend our previous study of the right arm of the 2nd chromosome to the left arm of the 2nd chromosome using the Bloomington deficiency kit’s set of large deletions, which collectively remove 98.9% of the genes on the left arm of chromosome two (2L) to identify ‘dorsal closure deficiencies’. We successfully screened 87.2% of the genes and identified diverse dorsal closure defects in embryos homozygous for 49 deficiencies, 27 of which delete no known dorsal closure gene. These homozygous deficiencies cause defects in cell shape, canthus formation and tissue dynamics. Within these deficiencies, we have identified pimples, odd-skipped, paired, and sloppy-paired 1 as dorsal closure genes on 2L that affect lateral epidermal cells. We will continue to identify novel ‘dorsal closure genes’ with further analysis. These forward genetic screens are expected to identify new processes and pathways that contribute to closure and links between pathways and structures already known to coordinate various aspects of closure.

2020 ◽  
Vol 32 (3) ◽  
pp. 541-552
Author(s):  
Mei Ling Jin

AbstractWe obtain approximation bounds for products of quasimodes for the Laplace–Beltrami operator on compact Riemannian manifolds of all dimensions without boundary. We approximate the products of quasimodes uv by a low-degree vector space {B_{n}}, and we prove that the size of the space {\dim(B_{n})} is small. In this paper, we first study bilinear quasimode estimates of all dimensions {d=2,3}, {d=4,5} and {d\geq 6}, respectively, to make the highest frequency disappear from the right-hand side. Furthermore, the result of the case {\lambda=\mu} of bilinear quasimode estimates improves {L^{4}} quasimodes estimates of Sogge and Zelditch in [C. D. Sogge and S. Zelditch, A note on L^{p}-norms of quasi-modes, Some Topics in Harmonic Analysis and Applications, Adv. Lect. Math. (ALM) 34, International Press, Somerville 2016, 385–397] when {d\geq 8}. And on this basis, we give approximation bounds in {H^{-1}}-norm. We also prove approximation bounds for the products of quasimodes in {L^{2}}-norm using the results of {L^{p}}-estimates for quasimodes in [M. Blair, Y. Sire and C. D. Sogge, Quasimode, eigenfunction and spectral projection bounds for Schrodinger operators on manifolds with critically singular potentials, preprint 2019, https://arxiv.org/abs/1904.09665]. We extend the results of Lu and Steinerberger in [J. F. Lu and S. Steinerberger, On pointwise products of elliptic eigenfunctions, preprint 2018, https://arxiv.org/abs/1810.01024v2] to quasimodes.


Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5195-5205 ◽  
Author(s):  
A.F. Ramsdell ◽  
H.J. Yost

The rightward looping of the primary heart tube is dependent upon upstream patterning events that establish the vertebrate left-right axis. In Xenopus, a left-sided Vg1 signaling pathway has been implicated in instructing cells to adopt a ‘left-sided identity’; however, it is not known whether ‘right-sided identity’ is acquired by a default pathway or by antagonism of Vg1 signaling. Here, we propose that an antagonistic, BMP/ALK2/Smad-mediated signaling pathway is active on the right side of the Xenopus embryo. Truncated ALK2 receptor expression on the right side of the blastula elicits heart reversals and altered nodal expression. Consistent with these findings, constitutively active ALK2 (CA-ALK2) receptor expression on the left side of the blastula also elicits heart reversals and altered nodal expression. Coexpression of CA-ALK2 with mature Vg1 ligand results in predominantly left-sided nodal expression patterns and normal heart looping, demonstrating that the ALK2 pathway can ‘rescue’ left-right reversals that otherwise occur following right-sided misexpression of mature Vg1 ligand alone. Results with chimeric precursor proteins indicate that the mature domain of BMP ligands can mimic the ability of the ALK2 signaling pathway to antagonize the Vg1 pathway. Consistent with the observed antagonism between BMP and Vg1 ligands, left-sided ectopic expression of Xolloid results in heart reversals. Moreover, ectopic expression of Smad1 or Smad7 identified two downstream modulators of the BMP/ALK2 signaling pathway that also can regulate cardiac orientation. Collectively, these results define a BMP/ALK2-mediated pathway on the right side of the Xenopus embryo and, moreover, suggest that left-right patterning preceding cardiac morphogenesis involves the activation of two distinct and antagonistic, left- and right-sided TGF(beta)-related signaling pathways.


BMJ ◽  
2004 ◽  
Vol 328 (7441) ◽  
pp. s112.4-s112
Author(s):  
Mohammad Al-Ubaydli

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.


BMJ ◽  
2004 ◽  
Vol 328 (7440) ◽  
pp. s102.5-s102
Author(s):  
Andrew Wilson

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BMJ ◽  
2004 ◽  
Vol 328 (7440) ◽  
pp. s102.4-s102
Author(s):  
Simon Eccles

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.


BMJ ◽  
2004 ◽  
Vol 328 (7442) ◽  
pp. s122.3-s122
Author(s):  
Susan Kersley

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BMJ ◽  
2004 ◽  
Vol 328 (7443) ◽  
pp. s132.2-s132
Author(s):  
Manoj Kumar

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BMJ ◽  
2004 ◽  
Vol 328 (7442) ◽  
pp. s122.5-s122
Author(s):  
Jim Bolton

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.


2020 ◽  
Vol 48 (14) ◽  
pp. 3454-3466
Author(s):  
Yang Chen ◽  
Yan Xu ◽  
Muzhi Li ◽  
Qiang Shi ◽  
Can Chen

Background: A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Hypothesis: Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Study Design: Controlled laboratory study. Methods: USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro–computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Results: Micro–computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group ( P < .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group ( P < .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group ( P < .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group ( P < .05 for all). Conclusion: A USC sheet was able to enhance RC healing in a canine model. Clinical Relevance: The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.


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