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

Author:

Cronk Katharine M.1,Wilkinson George A.2,Grimes Rachel3,Wheeler Esther F.3,Jhaveri Sonal4,Fundin Bengt T.5,Silos-Santiago Immaculada6,Tessarollo Lino7,Reichardt Louis F.7,Rice Frank L.1

Affiliation:

1. Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA

2. Neuroscience Unit, Howard Hughes Medical Center, University of California, San Francisco, CA 94143-0724, USA

3. Division of Life Sciences, University of Texas, San Antonio, TX 78249, USA

4. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

5. Astra Zeneca R&D Södertälje, Department of Molecular Sciences, SE-141 57 Huddinge, Sweden

6. Department of Neurobiology, Millennium Pharmaceuticals Inc., Cambridge, MA 02139-4815, USA

7. Neural Development Group, NCI-FCRDC, Frederick, MD 21702, USA

Abstract

This study demonstrates that innervation dependent on two different neurotrophin tyrosine kinase (trk) receptors can form the same types of sensory endings (Merkel endings) in the same target (Merkel cells of vibrissa follicles). Some endings transiently express trkA during their initial development, whereas others express trkC throughout their development. Consequently, elimination of kinase domains of either trkA or trkC each result in a partial loss of Merkel endings, whereas absence of kinase domains of both receptors results in a total loss. At the onset of Merkel ending development, at least one kinase-lacking trkC isoform is transiently expressed on all the follicle cells, while neurotrophin 3 is transiently expressed only in the cells at the middle third of the follicle where the Merkel endings and cells develop. This transient non-neuronal expression of truncated trkC is essential for development of any Merkel endings, whereas some Merkel endings and cells still begin to develop in the absence of neurotrophin 3. Therefore, truncated trkC plays a more important role in the development of this innervation than kinase forms of trkA or trkC or of NT3, the only known ligand for trkC receptors.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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