Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system.
BACKGROUND
During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A) is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS) and the central nervous system (CNS). Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS.


RESULTS
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.


CONCLUSIONS
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.
Mauti
Olivier
O
Developmental Neuroscience, Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Olivier.Mauti@zool.uzh.ch
Domanitskaya
Elena
E
Andermatt
Irwin
I
Sadhu
Rejina
R
Stoeckli
Esther T
ET
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D034622:RNA Interference; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D039961:Semaphorins; C091529:plexin