Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point.Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.During development of the nervous system, axons navigate long distances to connect to their targets. Along their trajectories they encounter a large variety of guidance cues that support their navigation [1,2]. Axon guidance cues are subdivided into long-range and short-range guidance cues. They belong to a relatively small number of protein families, the immunoglobulin superfamily of cell adhesion molecules [3], the Eph/ephrins [4], the netrins [5,6], the semaphorins [7,8] and their receptors, plexins and neuropilins [9,10]. More recently, morphogens such as Wnts and Shh have also been implicated in axon guidance [11-13].The semaphorins comprise a large family subdivided into eight subclasses based on structural criteria and their expression in vertebrates or non-vertebrate organisms [7,14,15]. Class 1 and 2 semaphorins are expressed only in invertebrates, classes 3, 4, 6, and 7 are expressed only in vertebrates, class 5 semaphorins are expressed in both invertebrates and vertebrates, whereas class V consists of a v