Deletion of the mouse RegIIIbeta (Reg2) gene disrupts ciliary neurotrophic factor signaling and delays myelination of mouse cranial motor neurons

Abstract

A large number of cytokines and growth factors support the development and subsequent maintenance of postnatal motor neurons. RegIIIβ, also known as Reg2 in rat and HIP/PAP1 in humans, is a member of a family of growth factors found in many areas of the body and previously shown to play an important role in both the development and regeneration of subsets of motor neurons. It has been suggested that RegIIIβ expressed by motor neurons is both an obligatory intermediate in the downstream signaling of the leukemia inhibitory factor/ciliary neurotrophic factor (CNTF) family of cytokines, maintaining the integrity of motor neurons during development, as well as a powerful influence on Schwann cell growth during regeneration of the peripheral nerve. Here we report that in mice with a deletion of the RegIIIβ gene, motor neuron survival was unaffected up to 28 weeks after birth. However, there was no CNTF-mediated rescue of neonatal facial motor neurons after axotomy in KO animals when compared with wild-type. In mice, RegIIIβ positive motor neurons are concentrated in cranial motor nuclei that are involved in the patterning of swallowing and suckling. We found that suckling was impaired in RegIIIβ KO mice and correlated this with a significant delay in myelination of the hypoglossal nerve. In summary, we propose that RegIIIβ has an important role to play in the developmental fine-tuning of neonatal motor behaviors mediating the response to peripherally derived cytokines and growth factors and regulating the myelination of motor axons.