The external granule layer of the developing chick cerebellum generates granule cells and cells of the isthmus and rostral hindbrain

The external granule layer (EGL) on the dorsal surface of the developing ce rebellum consists of neural progenitors originating from the rostral rhombi c lip (RRL). The RRL and the EGL were thought to give rise exclusively to t he granule neurons of the cerebellum (Alder et al., 1996). To study the fat e of individual RRL cells, we used a retroviral library to mark clones in t he chick embryo at Hamberger-Hamilton stages 10-12. RRL clones comprised th e EGL and cerebellar granule cells, as expected. Surprisingly, however, as many as 50% of the RRL clones also contained cells ventral to the cerebellu m proper. Ventral derivatives were found in clones with a medial origin, as well as in those with a lateral origin along the RRL. Some of the ventral progeny appeared to be in the process of migration, whereas others appeared to be differentiating neurons in the isthmus and the rostral hindbrain reg ion, including the locus coeruleus (LC) and pontine reticular formation. Fu rthermore, the Phox2a marker of LC precursors was detected in the EGL withi n the anterior aspect of the cerebellum. A stream of cells originating in t he EGL and expressing Phox2a was observed to terminate ventrally in the LC. These data demonstrate that single RRL progenitor cells are not restricted to producing only cerebellar granule cells; they produce both cerebellar g ranule cells and ventral derivatives, some of which become hindbrain neuron s. They also suggest that some progeny of the EGL escape the cerebellum via the anterior aspect of the cerebellar peduncles, to contribute to the gene ration of ventral structures such as the LC.