Formalización de un enfoque cuantitativo en el estudio de la organogénesis: caracterización de los límites morfológico-funcionales de órganos en insectos

Abstract

This thesis advocates for a quantitative approach in developmental biology, structured around a three-level analytical paradigm: (1) functional and subfunctional characterisation of organs, (2) analysis of developmental processes at defined observational scales, and (3) construction of predictive models sufficient to explain observed phenotypes. Across five case studies focusing on different organs and invertebrate species, this approach is shown to uncover robust regulatory mechanisms and key emergent properties of organ formation and function. The first two studies focus on the control of eye size in Drosophila melanogaster, revealing that size precision is an emergent property of development, actively maintained by a feedback mechanism mediated by apoptosis and regulated by BMP/Dpp signalling. Through the integration of theoretical models, cell-based computational simulations, and probabilistic frameworks, the work demonstrates that this control does not rely on an absolute size reference, but rather on the relative detection of developmental progress. Bilateral symmetry is employed as a proxy for autonomous control, enabling the distinction between intra- and inter-individual sources of variability, and providing functional evidence for the role of apoptosis in developmental stability. The third study examines the differentiation of the ocelli, simple sensory organs also present in Drosophila, where a polarised pattern of cell differentiation is driven by a stationary Hedgehog morphogen gradient. Using a mathematical model, the study shows that the precise and robust development of these organs arises from a local negative feedback mechanism, in which differentiated cells downregulate Ptc receptor expression, thereby dynamically modulating tissue sensitivity to the signal. The fourth study analyses the branching pattern of the tracheal system in the gills of Cloeon dipterum nymphs and other mayflies. Through the design of specific morphological metrics and a geometric space-colonisation algorithm, the work demonstrates that observed branching morphologies can be explained by simple developmental rules, consistent with the expression pattern of branchless, the insect homolog of FGF. Finally, the fifth study compares gene regulatory networks in Drosophila and Episyrphus balteatus, demonstrating that the robustness of retinal development in dipterans relies on a conserved core of transcription factors and regulatory elements. Using a computational strategy to infer regulatory interactions from chromatin accessibility and gene expression data, functional networks are reconstructed and compared across species, identifying both conserved elements and regulatory innovations linked to adaptive subfunctionalities. Together, these findings support the utility and applicability of the proposed quantitative paradigm for uncovering general principles governing organogenesis in complex biological systems-even in the absence of detailed molecular information-and provide new avenues for the comparative analysis of development and its evolution.