Diverse dependencies of developing Merkel innervation on the trkA and both full-length and truncated isoforms of trkC

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Sensory innervation involves complex interactions between neurons and target cells.
• Neurotrophins and their receptors, like tyrosine kinase (trk) receptors, mediate these interactions.
• Merkel endings, a type of sensory nerve ending, innervate Merkel cells in vibrissa follicles.

Purpose of the Study:

• To investigate the roles of trkA and trkC receptors in the development of Merkel endings.
• To determine the relative importance of different trk receptor isoforms and neurotrophin 3 (NT3) in this process.

Main Methods:

• Genetic manipulation to eliminate kinase domains of trkA and trkC receptors in vivo.
• Analysis of Merkel ending formation and survival in mutant mice.
• Examination of the expression patterns of trkC isoforms and NT3 during development.

Main Results:

• Both trkA and trkC signaling are necessary for complete Merkel ending development, with partial loss upon elimination of either.
• Absence of both trkA and trkC kinase domains leads to a total loss of Merkel endings.
• A kinase-lacking trkC isoform is essential for initial Merkel ending development, showing transient expression on follicle cells.
• Neurotrophin 3 (NT3) expression is restricted to the site of Merkel ending development, but its absence causes only a partial loss.

Conclusions:

• Development of Merkel endings relies on distinct roles for trkA and trkC signaling pathways.
• A truncated, non-signaling trkC isoform plays a critical, essential role in initiating Merkel ending formation.
• Truncated trkC has a more significant impact on Merkel ending development than signaling trkA, signaling trkC, or NT3.