Title
The spatiotemporal order of signaling events unveils the logic of development signaling.
Abstract
Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher thewell-appreciated but poorly defined logic of developmental signaling. Availability and implementation: The model is available upon request.
Year
DOI
Venue
2016
10.1093/bioinformatics/btw121
BIOINFORMATICS
Field
DocType
Volume
Drosophila Protein,Eye development,Biology,Hexagonal crystal system,Lateral inhibition,Signal transduction,Bioinformatics
Journal
32
Issue
ISSN
Citations 
15
1367-4803
0
PageRank 
References 
Authors
0.34
0
3
Name
Order
Citations
PageRank
Hao Zhu1111.72
Markus Owen2143.90
Yanlan Mao300.34