In vivo investigation of mitochondria in lateral line afferent neurons and hair cells.

To process sensory stimuli, intense energy demands are placed on hair cells and primary afferents. Hair cells must both mechanotransduce and maintain pools of synaptic vesicles for neurotransmission. Furthermore, both hair cells and afferent neurons must continually maintain a polarized membrane to propagate sensory information. These processes are energy demanding and therefore both cell types are critically reliant on mitochondrial health and function for their activity and maintenance. Based on these demands, it is not surprising that deficits in mitochondrial health can negatively impact the auditory and vestibular systems. In this review, we reflect on how mitochondrial function and dysfunction are implicated in hair cell-mediated sensory system biology. Specifically, we focus on live imaging approaches that have been applied to study mitochondria using the zebrafish lateral-line system. We highlight the fluorescent dyes and genetically encoded biosensors that have been used to study mitochondria in lateral-line hair cells and afferent neurons. We then describe the impact this in vivo work has had on the field of mitochondrial biology as well as the relationship between mitochondria and sensory system development, function, and survival. Finally, we delineate the areas in need of further exploration. This includes in vivo analyses of mitochondrial dynamics and biogenesis, which will round out our understanding of mitochondrial biology in this sensitive sensory system.

Transcriptomic analysis and ednrb expression in cochlear intermediate cells reveal developmental differences between inner ear and skin melanocytes.

In the inner ear, the neural crest gives rise to the glia of the VIII ganglion and two types of melanocytic cells: The pigmented cells of the vestibular system and intermediate cells of the stria vascularis. We analyzed the transcriptome of neonatal intermediate cells in an effort to better understand the development of the stria vascularis. We found that the expression of endothelin receptor B, which is essential for melanocyte development, persists in intermediate cells long after birth. In contrast, skin melanocytes rapidly downregulate the expression of EdnrB. Our findings suggest that endothelins might have co-opted new functions in the inner ear during evolution of the auditory organ.

Dhh-expressing Schwann cell precursors contribute to skin and cochlear melanocytes, but not to vestibular melanocytes.

For a long time, melanocytes were believed to be exclusively derived from neural crest cells migrating from the neural tube toward the developing skin. This notion was then challenged by studies suggesting that melanocytes could also be made from neural crest-derived Schwann cell precursors (SCPs) on peripheral nerves. A SCP origin was inferred from lineage tracing studies in mice using a Plp1 promoter-controlled Cre driver transgene (Plp1-CreERT2) and a fluorescent Rosa26 locus-controlled Cre reporter allele (Rosa26FloxSTOP-YFP ). However, doubts were raised in part because another SCP-directed Cre driver controlled by the Dhh promoter (Dhh-Cre) was apparently unable to label melanocytes when used with a non-fluorescent Rosa26 locus-controlled Cre reporter (Rosa26FloxSTOP-LacZ ). Here, we report that the same Dhh-Cre driver line can efficiently label melanocytes when used in a pure FVB/N background together with the fluorescent instead of the non-fluorescent Rosa26 locus-controlled Cre reporter. Our data further suggest that the vast majority of skin melanocytes are SCP-derived. Interestingly, we also discovered that SCPs contribute inner ear melanocytes in a region-specific manner, extensively contributing to the cochlea but not to the vestibule.