Primary cilia are critical for tracheoesophageal septation.

Introduction: Primary cilia play pivotal roles in the patterning and morphogenesis of a wide variety of organs during mammalian development. Here we examined murine foregut septation in the cobblestone mutant, a hypomorphic allele of the gene encoding the intraflagellar transport protein IFT88, a protein essential for normal cilia function.

Results: We reveal a crucial role for primary cilia in foregut division, since their dramatic decrease in cilia in both the foregut endoderm and mesenchyme of mutant embryos resulted in a proximal tracheoesophageal septation defects and in the formation of distal tracheo(broncho)esophageal fistulae similar to the most common congenital tracheoesophageal malformations in humans.

Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes.

Background: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting.

[Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes. German version].

Background: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting.

The emerging framework of mammalian auditory hindbrain development.

A defining feature of the mammalian auditory system is the extensive processing of sound information in numerous ultrafast and temporally precise circuits in the hindbrain. By exploiting the experimental advantages of mouse genetics, recent years have witnessed an impressive advance in our understanding of developmental mechanisms involved in the formation and refinement of these circuits. Here, we will summarize the progress made in four major fields: the dissection of the rhombomeric origins of auditory hindbrain nuclei; the molecular repertoire involved in circuit formation such as Hox transcription factors and the Eph-ephrin signaling system; the timeline of functional circuit assembly; and the critical role of spontaneous activity for circuit refinement.

The gene regulatory networks underlying formation of the auditory hindbrain.

Development and evolution of auditory hindbrain nuclei are two major unsolved issues in hearing research. Recent characterization of transgenic mice identified the rhombomeric origins of mammalian auditory nuclei and unraveled genes involved in their formation. Here, we provide an overview on these data by assembling them into rhombomere-specific gene regulatory networks (GRNs), as they underlie developmental and evolutionary processes.

Central auditory function of deafness genes.

The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context.

Multiple essential roles for primary cilia in heart development.

Background: The primary cilium is a microtubule-based, plasma membrane-ensheathed protrusion projecting from the basal bodies of almost all cell types in the mammalian body. In the past several years a plethora of papers has indicated a crucial role for primary cilia in the development of a wide variety of organs. We have investigated heart development in cobblestone, a hypomorphic allele of the gene encoding the intraflagellar transport protein Ift88, and uncovered a number of the most common congenital heart defects seen in newborn humans.

Primary cilia and forebrain development.

With a microtubule-based axoneme supporting its plasma membrane-ensheathed projection from the basal body of almost all cell types in the human body, and present in only one copy per cell, the primary cilium can be considered an organelle sui generis. Although it was first observed and recorded in histological studies from the late 19th century, the tiny structure was essentially forgotten for many decades. In the past ten years, however, scientists have turned their eyes once again upon primary cilia and realized that they are very important for the development of almost all organs in the mammalian body, especially those dependent upon the signaling from members Hedgehog family, such as Indian and Sonic hedgehog.

A crucial role for primary cilia in cortical morphogenesis.

Primary cilia are important sites of signal transduction involved in a wide range of developmental and postnatal functions. Proteolytic processing of the transcription factor Gli3, for example, occurs in primary cilia, and defects in intraflagellar transport (IFT), which is crucial for the maintenance of primary cilia, can lead to severe developmental defects and diseases. Here we report an essential role of primary cilia in forebrain development.

Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development.

Background: Dopaminergic neurons form in diverse areas of the vertebrate di- and mesencephalon to constitute several major neuromodulatory systems. While much is known about mammalian mesencephalic dopaminergic neuron development, little is known about the specification of the diencephalic dopaminergic groups. The transcription factors Pitx3 and Lmx1b play an important role in mammalian mesencephalic dopaminergic specification, and Nurr1/Nr4a2 has been shown to contribute to specification of the dopaminergic neurotransmitter phenotype.