Abstract
ABSTRACTVarious neurotransmitters influence neuronal migration in the developing zebrafish hindbrain. Migrating tegmental hindbrain nuclei neurons (THNs) are governed by depolarizing neurotransmitters (acetylcholine and glutamate), and glycine. In mature neurons, glycine binds to its receptor to hyperpolarize cells. This effect depends on the co-expression of the solute carrier KCC2. Immature precursors, however, typically express NKCC1 instead of KCC2, leading to membrane depolarization upon glycine receptor activation. As neuronal migration occurs in neurons after leaving the cell cycle and before terminal differentiation, we hypothesized that the switch from NKCC1 to KCC2 expression could alter the effect of glycine on THN migration. We tested this notion using in vivo cell tracking, overexpression of glycine receptor mutations and whole mount in situ hybridization. We summarize our findings in a speculative model, combining developmental age, glycine receptor strength and solute carrier expression to describe the effect of glycine on the migration of THNs.
Highlights
Neuronal migration is an essential developmental process contributing to the formation of a functional brain
We propose that NKCC1 is active in early-migrating tegmental hindbrain nuclei neurons (THNs), and that NKCC1 may play a role in regulating late-migrating THNs when glycine receptor signaling is over-active
We observed that excess glycine produces a mild decrease in THN speed in cells migrating in phase 2 along the MHB [3]
Summary
Neuronal migration is an essential developmental process contributing to the formation of a functional brain. Several external factors control migrating neurons, such as chemical and mechanical guidance cues. We have reported that neurotransmitters influence the migratory speed of tegmental hindbrain nuclei neurons (THNs) in live zebrafish embryos [3]. THNs emerge from a primordial zone, the upper rhombic lip (URL), to cross the developing cerebellum in a first phase to reach the midbrain-hindbrain-boundary (MHB) [4,5]. In a second migratory phase, the THNs follow the MHB ventrally to form clusters. Later in development, these neuronal clusters form the nucleus isthmi, the secondary gustatory/viscero-sensory nucleus, and the superior reticular nucleus [4]
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