Intestinal morphogenesis and homestasis

Metabolism and Cell Signaling
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

Our main scientific interest is the understanding of epithelial morphogenesis and polarity during morphogenesis, homeostasis and regeneration, as well as their implications in human diseases, such as intestinal bowel diseases (IBD), obesity, diabetes, and cancer. Our research is based is the organotypic culture model of three-dimensional epithelial cells growing in micropatterns “organ-on-a-chip”, which are becoming one of the best in vitro models systems for the investigation of epithelial morphogenesis. Moreover, with this system we are obtaining essential information about the molecular mechanisms that regulate epithelial morphogenesis. However, this model cannot reconstitute the complexity of the architecture given in vivo, which includes different cell types, dynamic remodeling and tissue homeostasis. For this reason, the use of in vivo systems should serve to validate and better characterize the phenotypes observed in vitro. We used the zebrafish and mouse intestine as models systems to elucidate epithelial morphogenesis and intestinal homeostasis.

We are focused on the analysis of genes that regulate epithelial polarity during morphogenesis and intestinal homeostasis, and particularly those controlling the following processes: membrane trafficking, mechanical forces and metabolic remodeling. Therefore, my lab is focused on:

-Characterization of signaling pathways for epithelial morphogensis, differantiation and patterning

-Analysis of cellular mechanics controlling lumen formation in epithelial cells

-Study of the metabolic reprogramming that takes place along intestinal development.

-Characterization of the metabolic crosstalk among microbiota, epithelial cells, and immune cells controlling the intestinal homeostasis.


Selected Publications:

1-Hachimi M, Campanario S, Rodriguez-Fraticelli A, Gomez-Lopez S, and Martin-Belmonte F. (2021) A network of actomyosin regulators controls apical maturation in epithelia. Current Biol S0960-9822(20)31685-7 .

2-Bosch-Fortea M, Rodriguez-Fraticelli A, Herranz G, Hachimi M, Ladoux B, Martin-Belmonte F. (2019) Micropattern-Based Platform as a Physiologically Relevant High-Throughput Model to Predict Nephrotoxicity of New Drugs. Biomaterials 18:119339.  

3-Bernascone I, Gonzalez T, Delgado M, Carabaña C, Hachimi M, Bosch-Fortea M, Santamaría S, Martin R, Tarnick J, García-Sanz JA, and Martin-Belmonte, F. (2019) Sfrp3 modulates stromal–epithelial crosstalk during mammary gland development by regulating Wnt levels. Nature Comm 10(1):2481.

-Bosch-Fortea M, and Martin-Belmonte F (2018) Mechanosensitive adhesion complexes in epithelial architecture and cancer onset. Current Opinion in Cell Biology 2018, 50:42–49

- Rodríguez-Fraticelli AE; Bagwell, J; Bosch, M; Reglero, N; García-.‐León, MJ, Andrés, G, Toribio, ML, Alonso, MA; Millan, J; Perez, F; Bagnat, M and Martín-Belmonte, F.  (2015) Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs. Nature Cell Biol 17:241-50

 - Bañón-Rodríguez, I; Gálvez-Santisteban, M; Vergarajauregui, S; Bosch, M; Borreguero, A and Martín-Belmonte, F. (2014) The control of IQGAP membrane localization by EGFR regulates mitotic spindle orientation during epithelial morphogenesis. EMBO J  1;33(2):129-45

- Bernascone, I and Martín-Belmonte, F. (2013) Transcriptional control of polarity. Trends Cell Biol. 23:380-9

-  Rodríguez-Fraticelli AE; Auzan, M; Alonso, MA; Bornens, M and Martín-Belmonte, F. (2012) Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis. Journal Cell Biology 198:1011-23.

-  Gálvez, M.A., Rodríguez-Fraticelli, AE; Vergarajauregui; Bañon, I, Bernascone, I; Fukuda, M; Mostov, KE and Martín-Belmonte F.  (2012) Synaptotagmin-Like Proteins Control Formation of a Single Apical Membrane Domain in Epithelial Cells. Nature Cell Biol 14:838-49.

- Martín-Belmonte F. and Mirna Perez-Moreno (2012) Epithelial cell polarity, stem cells and cancer. Nature Reviews Cancer  12:23-38.

Biomolecules & Cell D.
Molecular Biomedicine
Fernando Martin Belmonte