Tebar L A, Géranton S M, Parsons-Perez C, Fisher A S, Bayne R, Smith A J H, Turmaine M, Perez-Luz S, Sheasby A, De Felipe C, Ruff C, Raivich G, Hunt S P
National Centre for Cancer Research, Melchor Fernández Almagro, 3. E-28029 Madrid, Spain.
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11400-5. doi: 10.1073/pnas.0711978105. Epub 2008 Aug 4.
A large number of cytokines and growth factors support the development and subsequent maintenance of postnatal motor neurons. RegIIIbeta, 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 RegIIIbeta 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 RegIIIbeta 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, RegIIIbeta 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 RegIIIbeta KO mice and correlated this with a significant delay in myelination of the hypoglossal nerve. In summary, we propose that RegIIIbeta 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.
大量细胞因子和生长因子支持出生后运动神经元的发育及后续维持。再生胰岛衍生蛋白IIIβ（RegIIIβ），在大鼠中也被称为Reg2，在人类中被称为HIP/PAP1，是一类生长因子家族的成员，在身体的许多部位都有发现，此前已证明其在运动神经元亚群的发育和再生中都发挥着重要作用。有研究表明，运动神经元表达的RegIIIβ既是白血病抑制因子/睫状神经营养因子（CNTF）家族细胞因子下游信号传导中的一个必需中间体，在发育过程中维持运动神经元的完整性，也是外周神经再生过程中对雪旺细胞生长有强大影响的因子。在此我们报告，在缺失RegIIIβ基因的小鼠中，出生后28周内运动神经元的存活未受影响。然而，与野生型相比，基因敲除（KO）动物在轴突切断后，新生面部运动神经元没有得到CNTF介导的拯救。在小鼠中，RegIIIβ阳性运动神经元集中在参与吞咽和吮吸模式形成的颅运动核中。我们发现RegIIIβ基因敲除小鼠的吮吸功能受损，并将此与舌下神经髓鞘形成的显著延迟相关联。总之，我们提出RegIIIβ在新生儿运动行为的发育微调中发挥重要作用，介导对外周来源的细胞因子和生长因子的反应，并调节运动轴突的髓鞘形成。
