Abstract
The foxa regulatory gene is of central importance for endoderm specification across Bilateria, and this gene lies at an essential node of the well-characterized sea urchin endomesoderm gene regulatory network (GRN). Here we experimentally dissect the cis-regulatory system that controls the complex pattern of foxa expression in these embryos. Four separate cis-regulatory modules (CRMs) cooperate to control foxa expression in different spatial domains of the endomesoderm, and at different times. A detailed mutational analysis revealed the inputs to each of these cis-regulatory modules. The complex and dynamic expression of foxa is regulated by a combination of repressors, a permissive switch, and multiple activators. A mathematical kinetic model was applied to study the dynamic response of foxa cis-regulatory modules to transient inputs. This study shed light on the mesoderm–endoderm fate decision and provides a functional explanation, in terms of the genomic regulatory code, for the spatial and temporal expression of a key developmental control gene.
Original language | English |
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Pages (from-to) | 10103-10108 |
Number of pages | 6 |
Journal | PNAS |
Volume | 107 |
Issue number | 22 |
DOIs | |
State | Published - 2010 |
Externally published | Yes |
Keywords
- Cis-regulatory analysis
- Embryonic development
- Gene regulatory networks
- Mathematical modeling
ASJC Scopus subject areas
- General