Institute for Biology and Molecular Genetics
Thomas Schimmang

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FGF signalling

Functions of FGF genes during inner ear development and differentiation


The FGF genes comprise a large family of 24 growth factors which have been shown to act during a vast amount of processes including development, differentiation and regeneration. By conditional inactivation of FGF8 in distinct tissue compartments we have recently demonstrated that FGF8 is required in the mesoderm and endoderm during early inner ear development. In the chicken embryo, overexpression of FGF8 from various tissue sources during otic specification lead to a loss of otic tissue. In contrast ectopic overexpression of FGF10, a major player during murine otic induction, did not influence otic vesicle formation in chicken embryos but resulted in the formation of ectopic structures with a non-otic character. These studies underline the crucial role of a defined FGF8 expression pattern controlling inner ear formation in vertebrates. Recently we have examined the influence of Wnt signalling and its interaction with Fgf signalling on inner ear induction.

Recent publications:

V.S. Aggarwal, J. Liao, A. Bondarev, T. Schimmang, M. Lewandoski, J. Locker, A. Shanske, M. Campione and B. Morrow. (2006). Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy.
Hum. Mol. Genet. 15, 3219-3228.

L.C. Zelarayan, V. Vendrell, Y. Alvarez, E. Dominguez-Frutos, T. Theil, M.T. Alonso, M. Maconochie and T. Schimmang. (2007). Differential requirements for FGF3, FGF8 and FGF10 during inner ear development. 
Dev. Biol. 308, 379-91. 

X.P. Wang, M. Soumalainen, S. Felszeghy, L.C. Zelarayan, M.T. Alonso, M.V. Plikus, R.L. Maas, C.-M. Chuong, T. Schimmang and I. Thesleff. (2007). An integrated gene regulatory network controls stem cell proliferation in teeth. 
PLoS Biol. 5. e159

Schimmang T. (2007) Expression and functions of FGF ligands during early otic development.
Int J Dev Biol. 51, 473-81.

Delgado I, Domínguez-Frutos E, Schimmang T, Ros MA. (2008).The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death.
Dev Dyn. 237, 649-58.

Vázquez-Echeverría C, Dominguez-Frutos E, Charnay P, Schimmang T, Pujades C. (2008). Analysis of mouse kreisler mutants reveals new roles of hindbrain-derived signals in the establishment of the otic neurogenic domain.
Dev Biol. 322, 167-178.

Theil T, Dominguez-Frutos E, Schimmang T. (2008). Differential requirements for Fgf3 and Fgf8 during mouse forebrain development.
Dev Dyn. 237, 3417-3423

Tissue-specific requirements for FGF8 during early inner ear development. (2009). Domínguez-Frutos E, Vendrell V, Alvarez Y, Zelarayan LC, López-Hernández I, Ros M, Schimmang T.
Mech Dev. 126, 873-881.

V. Vendrell, C. Vázquez-Echeverría, I. López-Hernández, B. Durán Alonso, S. Martinez, C. Pujades and T. Schimmang. Requirements for Wnt8a during murine otic placode formation.


Instituto de Biología y Genética Molecular
Universidad de Valladolid - Consejo Superior de Investigaciones CIentíficas
C/ Sanz y Forés s/n
47003 - Valladolid - SPAIN
Phone: (+34) 983-184-818 Fax: (+34) 983-184-800

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