PT - JOURNAL ARTICLE AU - D. Aguilar-Hidalgo AU - D. Becerra-Alonso AU - D. García-Morales AU - F. Casares TI - Gene regulatory constraints to morphological evolution of the <em>Drosophila</em> ocellar region AID - 10.1101/031948 DP - 2015 Jan 01 TA - bioRxiv PG - 031948 4099 - http://biorxiv.org/content/early/2015/11/16/031948.short 4100 - http://biorxiv.org/content/early/2015/11/16/031948.full AB - The morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways and their regulatory interactions, which are represented by gene regulatory networks (GRNs). Therefore, the structure of an organ GRN constrains the morphological and functional variations that the organ can experience –its potential morphospace. Therefore, two important questions arise when studying any GRN: what is the predicted available morphospace and what are the regulatory linkages that contribute the most to control morphological variation within this space. Here, we explore these questions by analyzing a small "3 node”-GRN model that captures the Hh-driven regulatory interactions controlling a simple visual structure: the ocellar region of Drosophila. Analysis of the model predicts that random variation of model parameters results in a specific non-random distribution of morphological variants. Study of a limited sample of Drosophilids and other dipterans lends support to this prediction. As an alternative to simulations, we apply Bayesian Networks methods in order to identify the set of parameters with the largest contribution to morphological variation. Globally, our results support the concept that the topology of a GRN constrains the potential morphological space, defines this space and identify likely candidate processes to be responsible for ocellar morphological evolution using a novel method. We further discuss the assumptions that the approach we have taken entails and their validity.