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Hemangioblast Determination

by Jerry Rhee (Submitted: 02/26/2012)

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WHAT IS IT?

This model seeks to formalize the coordination of interactions that is required to generate blood and endothelial distribution patterns in the yolk sac at mouse headfold stages.
Specifically, it focuses on the requirements necessary to understand the stochastic interactions that influence hemangioblast determination, as marked by balanced nuclear HoxB4 and GATA1 levels, and its positioning.

HOW IT WORKS

Rules are modified from Ants and Slime.

All cells move based on their ability to sense a nutrition/chemical/food/ligand gradient at a specific distance from its current patch across a radial arc. The agents will then respond by moving towards the higher gradient in a probabilistic manner but are also constrained in the distance and angle of movement.

Some patches secrete chemicals. These patches are distributed across different regions; the blood islands (BI) are located at the top, oasis is the middle migration zone and the nook, an area marked by the arc of large triangle forms, which represents the contact region between the Ventral Cuboidal Mesothelium (VCM) and transitional visceral endoderm (AX) that sits close to the targets (epiblast/allantoic core domain (ACD)) at the bottom.

The targets are the source of new cells that migrate out of the epiblast or ACD. Green endothelial cells that do not have hematopoietic potential come out of the two large targets to generate the primary plexus. Large yellow clouds that represent hemangioblasts making the endothelial/erythroid choice come out of the little target. Each of these large clouds are assigned an initial value between 0 and 50 and adds a random value between 1 and 5 with each tick. When the difference gets greater than "threshold-difference", AND GATA1value > HOXB4value, then the cloud changes its color to red. If HOXB4value > GATA1value, the cloud changes to green, and becomes an angioblast. If it stays within the range of the "threshold-difference", it stays yellow, and thus, a hemangioblast.

HOW TO USE IT

steadyrate controls the rate of endothelial cell generation
HSCrate controls the rate of HSC generation
Divide1/Divide2 controls the type of endothelial cells that come out
All sliders below that aid in placing the chemical sources and their relative strengths.

All sniff and wiggle sliders control chemical sensing and movement response.

Threshold-difference determines at what range the choice between endothelial and erythroid cell is made.

On/Off hideturtle? switch controls whether you see the patch sources.

THINGS TO NOTICE

Where do the cells tend to congregate the most?

Do any two cells move together?

What's the spatial relationship between large yellow, green and red clouds over time?

THINGS TO TRY

Try making different arrangements. What's required to make those configurations? How is this environment produced in such a reproducible manner in the yolk sac? What actually executes these programs?

Chart the difference in specific cells over time.

Set an upper limit for threshold-difference based on cell distributions.

Set a lower limit for threshold-difference.

EXTENDING THE MODEL

Will adding adhesion rules change anything?

How about cell division rules?

RELATED MODELS

The patterns of movement of the endothelial cells and the blood cells and their ability to sense the chemical around them were adopted from the Ants and Slime models in the netlogo library.

CREDITS AND REFERENCES

To refer to this model in academic publications, please use: Wilensky, U. (1997). NetLogo Slime model. http://ccl.northwestern.edu/netlogo/models/Slime. Center for Connected Learning and Computer-Based Modeling, Northwestern University, Evanston, IL.
In other publications, please use: Copyright 1997 Uri Wilensky. All rights reserved. See http://ccl.northwestern.edu/netlogo/models/Slime for terms of use.

Rhee, Jerry M., Iannaccone, Philip M., Mapping mouse hemangioblast maturation from headfold stages, Developmental Biology (2012),
doi:10.1016/j.ydbio.2012.02.023

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