Background: Transgenic animals are widely used in biomedical research and biotechnology. Multicistronic constructs, in which several proteins are encoded by a single messenger RNA, are commonly used in genetically engineered animals. This is currently done by using an internal ribosomal entry site to separate the different coding regions. 2A peptides result in the cotranslational 'cleavage' of proteins and are an attractive alternative to the internal ribosomal entry site. They are more reliable than the internal ribosomal entry site and lead to expression of multiple cistrons at equimolar levels. They work in a wide variety of eukaryotic cells, but to date have not been demonstrated to function in transgenic mice in an inheritable manner.

SummaryThe inner ear and the epibranchial ganglia constitute much of the sensory system in the caudal vertebrate head. The inner ear consists of mechanosensory hair cells, their neurons, and structures necessary for sound and balance sensation. The epibranchial ganglia are knots of neurons that innervate and relay sensory signals from several visceral organs and the taste buds. Their development was once thought to be independent, in line with their independent functions. However, recent studies indicate that both systems arise from a morphologically distinct common precursor domain: the posterior placodal area. This review summarises recent studies into the induction, morphogenesis and innervation of these systems and discusses lineage restriction and cell specification in the context of their common origin. Key words: Epibranchial, Inner ear, Neurogenesis, Placode, Signalling IntroductionCranial placodes, found in all vertebrates, are transient thickenings of ectoderm that contribute extensively to the sensory component of the cephalic peripheral nervous system (see Box 1 and Glossary, Box 2). Individual placodes give rise to characteristic cell types, although the diversity of placodal derivatives varies (Box 1). Some placodes, such as the olfactory, otic and lateral line placodes, can form the receptive cell that responds to a stimulus, as well as the sensory neurons that transmit this information (Box 1). Others, such as the epibranchial and trigeminal placodes, only give rise to sensory neurons. The lens and adenohypophyseal placodes generate no sensory derivatives (Baker and Bronner-Fraser, 2001;Webb and Noden, 1993;Begbie and Graham, 2001b). In this review, we focus on the inner ear (or otic) placode and the epibranchial series of placodes and discuss their origins from a common progenitor domain: the posterior placodal area (PPA) (Fig. 1).The otic placode forms the complex inner ear structure that detects sound and balance, as well as the neurons that convey this information to the auditory hindbrain. The otic placodes form distinctive paired depressions adjacent to the caudal hindbrain and progressively deepen to form otocysts (see Glossary, Box 2). Transcriptional networks, influenced by extrinsic signals, drive the regional differentiation of the otic placode to generate mechanosensory hair cells, supporting cells and neurons (see Box 1 and Glossary, Box 2). This progressive differentiation results in a remarkable convolution of the simple spherical otocyst into an intricate structure that is dedicated to receiving information on balance, angular velocity and sound. These later morphogenetic events have been well reviewed (Bok et al., 2007;Fritzsch et al., 2006;Torres and Giráldez, 1998) and will not be covered here.The epibranchial placodes give rise to the geniculate, petrosal and nodose ganglia, which contribute sensory neurons to cranial nerves VII (facial), IX (glossopharyngeal) and X (vagus), in that order (see Box 1 and Glossary, Box 2; Fig. 1). Epibranchial placodes are located ventral to the...

Pharyngeal arches are a prominent and critical feature of the developing vertebrate head. They constitute a series of bulges within which musculature and skeletal elements form; importantly, these tissues derive from different embryonic cell types [1]. Numerous studies have emphasised the role of the cranial neural crest, from which the skeletal components derive, in patterning the pharyngeal arches [2-4]. It has never been clear, however, whether all arch patterning is completely dependent on this cell type. Here, we show that pharyngeal arch formation is not coupled to the process of crest migration and, furthermore, that pharyngeal arches form, are regionalized and have a sense of identity even in the absence of the neural crest. Thus, vertebrate head morphogenesis can now be seen to be a more complex process than was previously believed and must result from an integration of both neural-crest-dependent and -independent patterning mechanisms. Our results also reflect the fact that the evolutionary origin of pharyngeal segmentation predates that of the neural crest, which is an exclusively vertebrate characteristic.

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The cranial neural crest has long been viewed as being of particular significance. First, it has been held that the cranial neural crest has a morphogenetic role, acting to coordinate the development of the pharyngeal arches. By contrast, the trunk crest seems to play a more subservient role in terms of embryonic patterning. Second, the cranial crest not only generates neurons, glia, and melanocytes, but additionally forms skeletal derivatives (bones, cartilage, and teeth, as well as smooth muscle and connective tissue), and this potential was thought to be a unique feature of the cranial crest. Recently, however, several studies have suggested that the cranial neural crest may not be so influential in terms of patterning, nor so exceptional in the derivatives that it makes. It is now becoming clear that the morphogenesis of the pharyngeal arches is largely driven by the pharyngeal endoderm. Furthermore, it is now apparent that trunk neural crest cells have skeletal potential. However, it has now been demonstrated that a key role for the cranial neural crest streams is to organise the innervation of the hindbrain by the cranial sensory ganglia. Thus, in the past few years, our views of the significance of the cranial neural crest for head development have been altered.