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Left Right Asymmetry in Human Body
Transcript
Final Model
Ciliary Rotation: How?
Node: How?
Rotational Movement generates leftward flow. How?
Axial Tilt
- Results seem to converge on the "node"
- Node: a concave triangular region transiently formed during gastrulation at the ventral mid-line surface of early embryos
- Nodal pit celss have 1/2 cilia
- Ultrastructure very similar to that of immotile primary cilia
- What happends here? Next stage of this study!
The Morphogen X
Statistical Study
- Lack of KIF3 led to lack of cilia
- But how is absence of cilia related to randomness of LR asymmetry??
- Something related to ciliary rotation? Maybe. But how?
Studies on molecular motors of kinesin superfamily proteins (KIFs)
- Important parameters identified : generate simpler models to explain the essence of the underlying fluid mechanics
- Effect of the surface, or shear resistance, is the major factor responsible here
Hypothesis: Morphogen X is secreted into the extraembryonic fluid at ventral node, forms concentration gradient and
turns on the switch for the expression of genes that determine LR sy
How do cells in the embryo interpret nodal flow?
Chemical Response Model
How do cells in the embryo interpret nodal flow?
- Leftward flow in closed cavity should balance the rightward counterflow
- Advection by leftward flow dominates over diffusion and vice versa for right : material accumulation on the left side
Cellular Response Model
- Critique of earlier model, assumes flow itself physically invokes cellular responses
- Many cilia in peripheral region of ventral node are immotile: reinforcing the claim
- 2-cilia hypothesis: generation and sensing
Its Elementary,
Dr <insert surname here>!
The Case?
Nodal Vesicular Parcels
- Broke down the problem
- Understood the cause
- Answered all the whys and hows
- Inherent asymmetry in body
- Not random but organized asymmetry
- Why does this happen?
- How does the body 'know' about direction?
Kartagener's Syndrome
Crime Scene Samples!
- Formally studied in 1933, by (guess who?)
- Patients also suffered from sinusitis and bronchiectasis
- Defective cilia in their airway
- Defect in ultrastructures? Axonemes? Or purely genetic?
The Ones Who Helped
- Zimmer, Carl. “Growing Left, Growing Right.” The New York Times. The New York Times, 03 June 2013. Web. 03 June 2015.
- Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000.Axis Formation in Amphibians: The Phenomenon of the Organizer.
- Hirokawa, Nobutaka, Tanaka, Yosuke, Okada, Yasushi, and Takeda, Sen. “Nodal Flow and the Generation of Left-Right Asymmetry.” Cell 125.1 (2006): 33-45. Web.
- University of Pittsburgh Schools of the Health Sciences. “Team Identifies Mutations Associated with Development of Congenital Heart Disease.” Medical Xpress, Science X Network, 25 Mar. 2015. Web. 09 July 2015.
- Eggenschwiler, Jonathan T., and Kathryn V. Anderson. “Cilia and Developmental Signaling.”Annual review of cell and developmental biology 23 (2007): 345–373. PMC. Web. 3 July 2015.
- Juan, and Hamada. “Roles of Nodal-lefty Regulatory Loops in Embryonic Patterning of Vertebrates.” Genes to Cells : Devoted to Molecular & Cellular Mechanisms 6.11 (2001): 923-30. Web.
- Nakamura, Tetsuya, and Hiroshi Hamada. “Left-right Patterning: Conserved and Divergent Mechanisms.” Development (Cambridge, England) 139.18 (2012): 3257-62. Web.
- John Barnard, Dr. “Pediatric Research: Tiny Cilia Determine Body Symmetry.” The Columbus Dispatch. The Dispatch Printing Company, 10 May 2015. Web. 3 June 2015.
- http://brevia.hcura.org/the-internal-asymmetry-of-the-human-body/
- Left–right asymmetry in embryonic development: a comprehensive review, http://www.sciencedirect.com/science/article/pii/S0925477304002114
- http://www.nytimes.com/2013/06/04/science/growing-left-growing-right-how-a-body-breaks-symmetry.html?pagewanted=all&_r=0