Mechanisms of early patterning and neural specification during inner ear development

 

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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

functional organ?

 

Genetic manipulation, in vivo imaging, gene regulation approches are combined for a full understanding of the organogenesis process in zebrafish and other vertebrates.

Research Projects

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.


Publications

-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. 


-Mora N, Almudi I, Alsina B, Corominas M, Serras F (2012). The ss-amyloid protein precursor like (Appl) is a Ras1/MAPK regulated gene required for axonal targeting in Drosophila photoreceptor neurons. J Cell Sci. 2012 Nov 23. 


-Radosevic M, Robert-Moreno A, Coolen M, Bally-Cuif L and Alsina B (2011). Her9, a zebrafish Hes1 ortholog, represses neurogenic fate in the inner ear downstream of Tbx1 and RA. Development 138(3):397-408.


-Robert-Moreno A, Naranjo S, de la Calle-Mustienes E, Gómez-Skarmeta JL, Alsina B. (2010). Characterization of new otic enhancers of the pou3f4 gene reveal distinct signaling pathway regulation and spatio-temporal patterns. PLoS One. 5(12):e15907.


-Naranjo S., Voesenek K., de la Calle-Mustienes E., Robert-Moreno A., Kokotas H., Grigoriadou M., Economides J., Van Camp G., Hilgert N., Moreno F., Alsina B., Petersen M., Kremer H. , Gomez-Skarmeta, JL. (2010). Multiple enhancers located in a 1 Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing. Human Genetics 128(4):411-9.


-Abelló B, Khatri S., Scotting P., Giráldez F., Alsina B. (2010). Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling gradients determines the neurogenic and non-neurogenic domains in the otic placode. Dev Biol. 339(1):166-78. 

 


Present Members

Berta Alsina- Principal Investigator
Esteban Hoijman-postdoctoral fellow
Laura Fargas- PhD student
Davide Rubbini- PhD student
Laura Taberner- PhD student
part-time technicians: Marta Linares, Sara Calatayud
Past members

Undergraduate and Master Students: Jon Garrido, Maral Sebt, Cheasequah Blevins,
Postdoc:Alex Robert-Moreno
PhD:Marija Radosevic, Safia Khatri, Gina Abelló


Contact
Laboratory of Developmental Biology
Dept Experimental and Health Sciences
Universitat Pompeu FAbra-PRBB
Dr. Aiguader 88, 08003 Barcelona, Spain
Office: 328.02.04
office:+34-93 3160837
lab:+34-93 3160817
berta.alsina@upf.edu

How to reach the laboratory
We are located at the 3rd floor of the PRBB building (www.prbb.org). When you arrive ask for the Developmental Biology Laboratory. You can get to the PRBB building by metro (yellow line, L4), station Vila Olimpica-Ciutadella. 









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