Work

A Gene Network for Head Organizer Formation

Year: 2010
Type: dissertation
Abstract: The Spemann organizer determines the body plan, in its full variety of tissue components, normal proportion and placement. Although individual organizer's inducers responsible for head and trunk inductions have been identified, how these are handed out in perfect quantitative, spatial and temporal coordination remains enigmatic. Here we focused on the mechanisms establishing the organizer own architecture as key to explain such signaling coordination. We found that a crosstalk between two ligands emanating from the trunk organizer, Nodal and ADMP, defines a miniature anteroposterior axis. At its posterior pole, Nodal protects headinduction by competing ADMP for a shared receptor, ACVR2a; ADMP is allowed to signal more anteriorly to restrain these inductions. These opposing signaling centers reciprocally adjust their strength and range of activity by multiple negative and positive loops. In so doing, the levels of head inducers remains proportional to signals generated in the trunk and buffered against their fluctuations. Several new regulatory elements are essential for this dynamic crosstalk, including a microRNA, miR-15/16, endowing robustness to head formation. In sum, we propose a model that offers a molecular explanation for key properties of the Spemann's organizer.
Language: English
Open Access status: green
OpenAlex ID: W143015179
Cites: 53
Cited by:
Related to: 10