RESEARCH

   Scutoids are Nature solution to 3D epithelial packing


   Epithelial cells have been traditionally depicted as prisms with polygonal apical and basal faces. Recently, we have obtained surprising results that change this paradigm, and provide a more realistic framework to understand and explain the architecture of epithelia. We have found in a number of different epithelia, that cells exchange their neighbours along the apico-basal axis. Importantly, this phenomenon is incompatible with the traditional view of epithelial cells as prisms, and compels the cells to adopt a new geometrical shape that we name  “scutoids”. Strikingly, in collaboration with Dr Javier Buceta we developed a biophysical model that suggests that scutoids contribute to minimize the energy of the tissue. Altogether, we conclude that scutoids are required for epithelial bending.

   We plan to investigate how this new framework affects different processes in development and disease to shed light on the biomechanical mechanisms of organ morphogenesis and maintaining.

   In the different aspects of this project we collaborate with the labs of Dr Javier Buceta (Lehigh University), Dr Alberto Márquez and Dr Clara Grima (Seville University), Dr Sol Sotillos (CABD, Seville) and Dr Yanlan Mao (UCL, London).
A) Cells are simplified as prisms in planar epithelia. B) Scheme representing an invagination or fold in a monolayer epithelium. Cells adopt the called “bottle shape” that would be simplified as frusta. C) Three-dimensional reconstruction of four cells in a curved epithelium. Green, yellow, blue and red cells present an apico-basal transition. The green and red cells contact in the basal part. D) The blue and yellow cells contact in the apical part, but not in the basal part. E) Two schemes for scutoids solids that are characterized by having curved surfaces and at least a vertex in a different plane to the two bases.


    Topological analysis of postnatal muscle development in mouse.


   The diagnosis of neuromuscular diseases is strongly based on the histological characterization of
muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. A few years ago, we developed NDICIA, a method that extract useful information from muscle samples in an objective, automated, fast and precise manner. NDICIA quantification of the severity of muscular dystrophies strongly correlates with the evaluation of the degree of affectation carried out by the pathologist.

   Now we have improved NDICIA to adapt it to mice biopsies. We are obtaining muscle biopsies from different time-points of mouse postnatal development to examine geometric and organizational (network characteristics) features. Our aim is to identify the developmental changes that raise the adult functional muscle. In parallel we are analysing the Amiotrophic Lateral Sclerosis mouse model (G93A-SOD1 transgene). The objective is to quantitatively compare these images looking for characteristics that define each stage and identify the first pathological signs in the SOD1 mouse.

  In  this project we work very closely efforts with the lab of Dr Carmen Paradas (IBiS). We have formed and interdisciplinary team and joined the Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.

    Mathematical analysis of neuroblastoma extracellular matrix



   Neuroblastoma is the most common solid tumour and despite major improvements in the cure rate for other pediatric tumours, the survival rate for patients with neuroblastoma is low. Imaging technology is key for the accurate quantification of pathology specimens.

 The tumour microenvironment has a strong influence on cancer malignancy. We investigate whether the organization of the extracellular matrix glycoprotein vitronectin in the tumour stroma may confer mechanical properties affecting neuroblastoma aggressiveness. Combining image analysis and graph theory, we identify two topological features of vitronectin that could potentially be used to improve patient pre-treatment risk stratification. Our data also point to the creation of vitronectin migration tracks for malignant neuroblasts, so that dramatic changes in the extracellular matrix would increase tumour stiffness and aggressiveness and worsen patient outcomes.

This project is funded by the Fundación Asociación Española Contra el Cancer in collaboration with the lab of Dr Rosa Noguera from INCLIVA (Valencia).