Regulatory analysis of the mouse Fgf3 gene: control of embryonic expression patterns and dependence upon sonic hedgehog (Shh) signalling.

Fgf3 displays a dynamic and complex expression pattern during mouse embryogenesis. To address the molecular mechanisms underlying Fgf3 expression, we used a transgenic approach to assay genomic regions from the mouse Fgf3 gene for regulatory activity. We identified an enhancer that mediates major components of embryonic expression, governing expression in the midbrain, hindbrain, surface ectoderm, dorsal roots and dorsal root ganglia (DRG), proximal sensory ganglia, and the developing central nervous system (CNS).

Identification and analysis of genes from the mouse otic vesicle and their association with developmental subprocesses through in situ hybridization.

The otic vesicle (otocyst) occupies a pivotal position in inner ear development, bridging the gap between otic placode determination, and morphogenesis of vestibular and auditory compartments. The molecular mechanisms underlying the progressive subdivision of the developing inner ear into different compartments, and the molecular control and execution of the different developmental processes involved, are largely unknown. Since relatively few genes have been implicated in these processes, we have undertaken this study to identify genes involved in these early embryonic stages.

Analysis of genes from inner ear developmental-stage cDNA subtraction reveals molecular regionalization of the otic capsule.

Although the gross embryology of inner ear development has been documented for several different vertebrate species at a descriptive level, our understanding of the molecular mechanisms involved remains rudimentary. Therefore, we have used cDNA subtraction and normalization procedures to define genes upregulated in the 13.5dpc mouse inner ear, a developmental stage where inner ear morphogenesis and tissue remodeling is active and differentiation of future hair cells is being initiated.

Determination of downstream targets of FGF signalling using gene trap and cDNA subtractive approaches.

Signalling through the fibroblast growth factor family (FGF) of ligands is essential for normal mammalian embryonic development. At a cellular level, many details of the molecular basis of the signal transduction process have been uncovered, but our knowledge of the identity of the downstream effectors of the FGF signal in the developing embryo remains limited. We have used two independent approaches to begin to identify downstream targets of FGF signalling in the embryo: (1).

Sonic hedgehog signaling from the urethral epithelium controls external genital development.

External genital development begins with formation of paired genital swellings, which develop into the genital tubercle. Proximodistal outgrowth and axial patterning of the genital tubercle are coordinated to give rise to the penis or clitoris. The genital tubercle consists of lateral plate mesoderm, surface ectoderm, and endodermal urethral epithelium derived from the urogenital sinus.