Our laboratory is interested in the regulation of cell renewal, tissue remodelling and the acquisition of specific cell fates
in a spatio-temporal order during organogenesis. We focus on the development of the inner ear to understand the signals
and cellular events that lead to the senses of hearing and balance. Which signals allow the precise pattern of sensory
neurons and hair cells, are does re-used during regeneration, how is patterning coupled with morphogenesis for a
Genetic manipulation, in vivo imaging, gene regulation approches are combined for a full understanding of the organogenesis process in zebrafish and other vertebrates.
1) Inner ear morphogenesis
The inner ear is one of the most complex three-dimensinal organs of our head, however it still a mistery how cells organize during development to generate this complex organ. We are studying several morphogenetic events to understand the interaction between cell polarity, cell remodeling, migration and cytoskeleton rearrangements with mechanical properties. In particular, we focus on the process of formation of an intra-organ cavity, neuron delamination and placode assembly.
2) Axial patterning and specification of a neurosensory domain
During inner ear development, a wide array of signals form surrounding tissues impinge on the ear primordium and activate a set of transcription factors (TF). We are investigating the gene regulatory networks involved in the development of hair cells and sensory neurons. In particular, we focus of FGF, Notch and RA signaling and the TF downstream of these pathways directing cells to the various cell fates at precise locations and times.
3) Molecular mechanisms of Hair Cell regeneration
While mammalian vertebrates cannot regenerate damaged hair cells, this ability has been retained in non-mammalian vertebrates. We are studying in zebrafish the role of RA pathway in hair cell regeneration.
4) Links between development and disease
Defects on essential genes involved in inner ear development, result in deafness and vertigo. Currently, are investigating the role of Sall1 in deafness and the role of fluid regulation during lumen formation for ear function.
-Hoijman E, Rubbini D, Colombelli J, and Alsina B (2015). Mitotic cell rounding and epithelial thinning regulate lumen growth and shape. Nature Commun 6:7355 DOI 10.1038
-Iturbide A, Pascual-Reguant L,Fargas L, Cebrià JP, Alsina B, García de Herreros A, and Peiró S (2015). LOXL2 oxidizes methylated TAF10 and controls TFIID-dependent genes during neural progenitor differentiation. Mol Cell 58(5):755-66. doi: 10.1016/j.molcel.2015.04.012.
-Radosevic M, Fargas L and Alsina B (2014). The role of her4 in inner ear development and its relationship with proneural genes and Notch signalling. PLoS One, 9(10):e109860. doi: 10.1371
-Maier EC, Saxena A, Alsina B, Bronner ME, Whitfield TT (2014). Sensational placodes: Neurogenesis in the otic and olfactory systems. Dev Biol 126(Pt 1):53-9.