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Table of contents
Introduction
1- Mechanics in development
a- Forces in biology
b- Forces of embryonic development
2- Mechanotransduction
I – Mechanotransduction in Drosophila embryo mesoderm invagination: transition from individual pulsating to collective constriction apex behaviour
1- Introduction
a- Drosophila embryo mesoderm invagination
b- Existing models of gastrulation
2 – The Snail/Fog patterned mechanosensitive model: a 1 Dimension model
3- Simulation’s results
a- Quantitative phenocopy of experimental constriction dynamics by in silico modelling
b- Passive and active collective behaviours
c- A critical role for the frequency of Snail dependent pulsations
d- The alternative hypothesis of a mean field hydrostatic pressure
4- Conclusion
a- The mechanosensitive model quantitatively phenocopies experimental apex constriction dynamics
b- Physiological function of collective constriction transition
c- Constriction transition leading to mesoderm invagination as emerging from ‘mechano-genetic’ coupling in development
5- Perspectives
II- Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria
1- Introduction
a- Zebrafish development
2- notail induction at the onset of epiboly
a- notail expression is β-cat dependent
b- β-cat -dependent notail expression is Wnt-independent
3- Mechanical induction of β-cat nuclear translocation in mesoderm cells
4- Mechanical induction of notail expression
5- Mechanical induction of β-cat dependent ntl expression by magnetic forces quantitatively mimicking the onset of epiboly dynamics
6- Mechanical induction of β-cat molecular translocation and of ntl expression by Y667 β-cat phosphorylation
7- Pathways synergising with Y667-β-cat mechanically induced phosphorylation
a- Bmp and Nodal
b- Mapk and phospho-GSK3β
8- Comparison with Drosophila and evolutionary consequences
a- Mechanical induction of Twist expression by Armadillo/ β-cat nuclear translocation
b- Mechanical induction of Y667 β-cat phosphorylation
9- Conclusion: a mechanotransductive origin of mesoderm emergence in the common ancestor of bilaterians ?
10- Perspectives
III- Mechanically Induced Heritable Modulation of Developmental Biochemical Regulation
1- Introduction
a- Epigenetics in Drosophila
b- The pi-RNA transposon repressing complex
c- The checkpoints DNA integrity guardians
2- Mechanically induced herited early developmental phenotypic defects
a- Mortality and morphological approach to study the progeny
b- Inheritance of anomalies in the progeny of indented embryos
c- Microscope analysis
3- Hypothesis: the dorsalised phenotype as induced by checkpoint activation
a- Dorsalized ventro-dorsal gradient of Dorsal nuclear translocation
b- Testing the inhibition of the check point phenotype by indenting p53 and Check-2 mutants
4- Testing the transposon activation hypothesis
a- Candidate approach
b- Non-candidate screening approach
5- Conclusion
a- Genetic transmission
b- Epigenetic transmission
6- Perspectives
a- Transposon activation
b- Individual flies sequencing
c- Physical characterization of the underlying mechanotranductive process
d- Putative speciation process
General conclusion
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