The rhombic lip is a posterior section of the developing metencephalon which can be recognized transiently within the vertebrate embryo. It extends posteriorly from the roof of the fourth ventricle to dorsal neuroepithelial cells. The rhombic lip can be divided into eight structural units based on rhombomeres 1-8 (r1-r8), which can be recognized at early stages of hindbrain development. Producing granule cells and five brainstem nuclei, the rhombic lip plays an important role in developing a complex cerebellar neural system.
History Through studies of human embryos performed in the late 1890s, Swiss anatomist Wilhelm His identified a portion of hindbrain neuroepithelium that was distinct from the rest of the hindbrain neuroepithelium in its morphology, sustained chromosomal division into late stages of embryogenesis, and deployment of streams of neurons through the hindbrain periphery. His named this zone "rautenlippe," or rhombic lip, because it seemed to emanate from the rhomboid-shaped opening of the fourth ventricle, much like the shape of a mouth. His proposed that the rhombic lip held the precerebellar precursors that would migrate ventrally to populate the pontine and olivary nuclei, but the methodologies available at the time limited the amount of evidence he could gather. The first real evidence that precerebellar neurons had a dorsal origin was obtained in the 1990s through the use of chick-quail chimeras, a technique in which portions of quail hindbrain neuroepithelium are grafted into chick embryos in ovo. Tracking the ventral migration of the quail daughter cells confirmed His' theory.
Development
Origin of cerebellar territory The cerebellum, or "little brain," is a portion of the brain attached to the brainstem at the pons. Among other functions, it is important for balance, coordinating movement, and maintaining muscle tone. The outer layer of the cerebellum, the cortex, is made up of three layers containing two classes of neurons. One of these classes has been identified as granule cells, which are produced by the rhombic lip. Genes FGF8 and EN1 play an important role in patterning the midbrain and hindbrain regions. In particular, studies have shown that different dosages of FGF8 appear to specify the tectum or cerebellum: regions exposed to strong dosages of FGF8 acquire cerebellar characteristics while regions exposed to weak dosages become the tectum.
Cellular contribution of the rhombic lip Neural specification in the cerebellum begins as a symmetric bulge in the fourth ventricle. Around embryonic days nine to eleven, cells arise from two areas: the rhombic lip and the ventricular zone. The rhombic lip produces glutamatergic granule neurons (which evolve from r1) and the five brainstem nuclei (thought to evolve from r6-r8). One brainstem nucleus, the inferior olivary nucleus, projects climbing fibers to innervate Purkinje cells. The other four nuclei (the external cuneate nucleus, the lateral reticular nucleus, the pontine nucleus, and the thalamic reticular nucleus) project mossy fibers to innervate granule neurons. Meanwhile, cells in the ventricular zone evolve into GABAergic Purkinje cells (another type of cerebellar neuron) and deep cerebellar nuclei.
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