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Principal investigator Dr. Alsina  

G. Abelló, S. Khatri, B. Alsina

The senses of hearing, gravity, linear and angular acceleration are perceived by the inner ear, a cranial sensory organ that conveys these external stimuli to the central nervous system. A central question in developmental biology is to understand how, during the development of the embryo, a homogeneous tissue is patterned and subdivided to generate all the containing parts in their precise locations.

The first cells to be specified during inner ear development are the precursors of sensory neurons as revealed by the expression of Neurogenin1 and Delta1 (Henrique et al., 1995; Adam et al., 1998; Alsina et al., 2004). Neurogenesis only takes place in the anterior lateral region of the otic primordium, what is called the proneural domain. We are interested in the first signs of otic regionalization in connection with the segregation of the proneural domain of the otic placode. How and when is the proneural domain established? Which genes are relevant for its development?

Our main interests are to understand how patterning of the otic placode takes place and how otic neural induction takes place.

Search for genes involved in the specification of neural and non-neural compartment

Two complementary domains are detected at the onset of otic placode formation and these regions coincide with a neural and a non-neural region. Which genes participate in the specification of both territories? Is neurogenesis supressed in the non-neural region? We are currently investigating the role of Lmx1b, Tbx1 in the non-neural domain, as well as the role of Sox genes in neural specification. In parallel we are undertaking a molecular approach to identify new genes involved in early otic patterning.

Role of Notch signaling in early otic patterning


Notch signaling has been suggested to control several developmental process from cell fate specification to patterning and boundary formation. Notch signaling mediators are differentially expressed in the neural and non-neural territory indicating a possible role in early patterning. To test the role of Notch signaling pathway in neural and non-neural otic developement we have performed gain of funtion and loss of function experiments which indicate that Notch signaling is required for regulating the expression of Lmx1 and Irx1 in the anterior doamin ( Abello et al., Mech Dev. 2007 Apr 20; [Epub ahead of print]).

Mechanism of delamination in the intersection neural/non-neural

Neuroblasts delaminate at the posterior border of the neural territory. it can be hypothetized that the restriction of mixing of cells from neural/non-neural region helps delamination. We are investigating the adhesion molecules that could be responsible for the segregration of neural and non-neural territories and their relation to neuroblast migration.
 
 

Group members

 

Publications

Abelló G., Giráldez F., Alsina B. (Mech Dev. 2007 Apr 20). Early regionalization of the otic placode and its regulation by the Notch signaling pathway.

Neves, J., Kamaid, A., Alsina, B., Giráldez, F. (2007). Differential expression of Sox2 and Sox3 in neuronal and sensory progenitors of the developing inner ear of the chick. J. Comp. Neurol.. 503(4):487-500.
Pujades, C., Alsina, B., Giráldez, F. (2006). BMP4 regulates the development of hair-cells by modulating progenitor cell survival. Dev. Biol. 292(1):55-67.

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.

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.

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.

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