Development and Developmental Disorders of the Brain Stem

The brain stem is composed of the midbrain (the mesencephalon) and the hindbrain (the rhombencephalon), and is, at least during development, segmentally organized. The midbrain is composed of two temporarily present segments known as mesomeres, whereas the hindbrain is composed of eight, and more recently of 12, rhombomeres (r0-r12), counting the isthmic rhombomere as r0. The cerebellum arises from the first and second rhombomere (r0 and r1). The brain stem also contributes 10 of the 12 cranial nerves, III-XII. A great number of genes are involved in the proper development of the brain stem. The isthmus organizer regulates the early development of the mesencephalon and of the rostral part of the rhombencephalon. Each rhombomere is characterized by a unique combination of Hox genes, its Hox code. In mice, spontaneous and targeted (knockout) mutations in these genes result in specific, rhombomere-restricted disruptions in the development of motor nuclei of cranial nerves. Such a “rhombomeropathy” has been described for the HOXA1 gene. In this chapter, patterning of the brain stem and its segmentation are discussed in • Sect. 7.2, followed by an overview of the development and developmental disorders of the cranial nerves (• Sect. 7.3). In • Sect. 7.4, the development of the auditory system, its molecular basis, some of its disorders, and genes associated with deafness are discussed. Clinical cases illustrate some major malformations.