| Principal investigator Dr. Giraldez |
The vertebrate inner ear is responsible for the senseof hearing, balance and acceleration. From its originas a single placode, the inner ear becomes a complex labyrinth of exquisite geometry that holds mechano-transducing receptor cells and the sensory neurons that convey the information to the central nervous system. Both sensory receptors and neurons derive from the otic placode.
Fundamental problems in ear development are, for example, the molecular and cellular mechanisms of sensory neuron generation, the signalling pathways involved in inducing a neuronal versus sensory fate and the relationship of cell fate and cell proliferation.
Role of extrinsic factors in neurosensory development
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We are interested in understanding the role of cell communication signals in cell fate acquisition and progenitor renewal. For this purpose we work in explants of otic vesicles and culture them in controlled media with BMPs, BMP antagonists and FGFs. The interplay between intrinsic and extrinsic factors is essential for the transit into different cell states during development. We are currently studying the interactions between FGFs, BMPs, atonal-like proneural, and neurogenic (delta/notch) gene families in the specification of neuroblasts and sensory precursors. We have recently shown that FGF10 is expressed in the proneurosensory (proNS) domain throughout ear development and FGF signaling is required for the determination of otic neuroblasts in the chick embryo (Alsina et al., 2003). Later in development, blockade of BMP4 signaling is required for sensory precursors differentiation (Pujades et al., 2006).
Coordination of cell fate acquisition and the cell-cycle
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To understand how extrinsic factors promoting sensory fate can regulate the cell-cycle, we are currently studying the effects of extrinsic factors as for example BMPs, RA and FGFs on proliferation and specific cell-cycle markers. .
Study of sensory progenitors during the development of the inner ear
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Sox proteins are transcription factors of the Sry protein family that have been shown to be crucial for neural development. SoxB1 proteins are expressed in self-renewing neuroepithelial progenitors. Sox proteins are being used as markers of progenitor state for otic development. In vivo experiments and experiments of cell culture are being carried out to investigate the transition of the progenitor state to the different otic cell types.Publications
Torres, M. and Giraldez, F. (1998). The development of the vertebrate inner ear. Mech. Dev. 71, 5-21. (Journal Club in TINS 23:332 "Ear rings: FGF3 comes full circle", by D. Fekete)
Vendrell, V., Carnicero, E., Giraldez, F., Alonso, M. T. and Schimmang, T. (2000) Induction of inner ear fate by FGF-3. Development 127, 2011-2019.
Camarero G., Leon Y. , Gorospe I., De Pablo F., Alsina B., Giráldez F. and Varela-Nieto I. (2003). Insulin-like growth factor 1 is required for survival of transit-amplifying neuroblasts and differentiation of otic neurons. Dev.Biol. 262:242-253.
Alsina B. , Giráldez F. and Varela-Nieto I. (2003). Growth factors and early development of otic neurones: interactions between intrinsic and extrinsic signals. Current Topics in Developmental Biology. Development of the Auditory and Vestibular Systems. Molecular Development of the Inner Ear. Academic Press. Edited by R. Romand and I. Varela-Nieto, 6, 177-206.
Alsina B., Abelló G. , Ulloa E., Henrique D., Pujades C., Giráldez F. (2004). FGF signaling is required for determination of otic neuroblasts in the chick embryo. Dev. Biol. 267:119-134.
