Essential role of stem cell factor signaling in primary sensory neuron development.
Here we show that stem cell factor (SCF) signaling through its receptor, c-kit, is essential for the development of c-kit-expressing small- and medium-diameter primary sensory neurons. We used the W mouse, which is c-kit deficient and has a perinatal lethal phenotype due to a naturally occurring point mutation in the c-kit gene. In c-kit-null newborn mice, 52.5% of substance P immunoreactive and 31.4% of calcitonin gene-related peptide (CGRP) immunoreactive small- and medium-diameter sensory neurons were absent, whereas large-diameter sensory neurons were unaffected. Equivalent deficits occurred during embryogenesis. There was neither a developmental delay nor degeneration of differentiated neurons. We thus conclude that, in the absence of SCF signaling, neural crest-derived progenitors do not differentiate into c-kit-expressing visceral and somatic afferent neurons.
Zhang
Zhi-Jian
ZJ
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, USA.
Sieber-Blum
Maya
M
D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000196:embryology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D055495:Neurogenesis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019089:Stem Cell Factor / Q000378:metabolism*; D013373:Substance P / Q000096:biosynthesis
D019089:Stem Cell Factor; D013373:Substance P; D019009:Proto-Oncogene Proteins c-kit; D015740:Calcitonin Gene-Related Peptide