Schwann cells are not required for guidance of motor nerves in the hindlimb in Splotch mutant mouse embryos

Abstract

The topogenesis of the hindlimb nerves of Splotch homozygous mutant mouse embryos was studied using light and electron microscopy. Homozygous mutants show multiple defects of neural crest-derived tissues. The defects increase along a rostro-caudal gradient. The cervical and upper thoracic segments have small spinal ganglia, and Schwann cells are associated with the spinal nerves. In the lumbo-sacral region neurulation is not complete, and the derivatives of the neural crest are missing. The lumbo-sacral nerve trunks are formed by ventral roots only. They are occasionally associated with presumptive glial cells that have migrated from the spinal cord for a short distance. Beyond the vertebral primordia, the spinal nerves are not accompanied by Schwann cells. No compartmentalization of the axons within the lumbo-sacral nerves was visible, whereas Schwann cells did segment the nerve into the fascicles in brachial nerves. The lumbo-sacral plexus develops, and its branches grow into the hindlimb despite the absence of Schwann cells. On day 13.5 of gestation, the lumbo-sacral nerve trunks extend well into the distal calf. They are topographically correctly positioned. Their branches enter the muscle primordia and form contacts with their mesenchymal cells though the cutaneous branches are missing. Generally, the outgrowth of lumbo-sacral nerves is slower than in phenotypically normal littermates, whose nerves reach the foot plate at corresponding stages of development. These results demonstrate that the lumbo-sacral plexus and the topographically correct position of lumbo-sacral nerve trunks develop despite the absence of Schwann cells. Therefore Schwann cells are not necessary for the outgrowth and guidance of axons within the limb.

Schwann Cells: Development and Role in Nerve Repair

“…This can be seen in mice with genetic inactivation of neuregulin signaling, in which nerves follow a normal position and trajectory from the spinal cord toward their targets, although they lack Schwann cell precursors and are essentially composed only of axons (Meyer and Birchmeier 1995;Morris et al 1999;Woldeyesus et al 1999). In agreement, motor nerves grow correctly toward their targets in Splotch (Pax3) mouse mutants, although both Schwann cell precursors and DRG sensory axons are missing (Grim et al 1992). Comparable observations have been made in other models (Keynes 1987), including zebrafish, in which initial outgrowth and guidance of axons in the lateral line is normal without glia (Raphael and Talbot 2011).…”

Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking Glial Cells

“…To address this question, one needs to know first if Schwann cells are necessary during the initial navigation of axons to their target muscles (Keynes 1987). It has been shown that motor axons can reach their target muscles and even form the initial nerve-muscle contacts, albeit only transiently, in mutant mice of ErbB2 (Morris et al 1999;Woldeyesus et al 1999;Lin et al 2000), ErbB3 (Riethmacher et al 1997), and Splotch (Grim et al 1992) mutant mice, all of which lack Schwann cells in the peripheral nerves. Furthermore, functional nervemuscle contacts can be formed in cultures without Schwann cells (Kullberg et al 1977;Chow and Poo 1985).…”

The Splotch mutation interferes with muscle development in the limbs

“…Homozygosity of the Splotch mutation (Sp) on chromosome I of the mouse causes defects in the closure of Correspondence to : T. Franz the neural tube (Auerbach 1954) and defects in neural crest-derived tissues such as pigment cells (Auerbach 1954), spinal ganglia (Auerbach 1954;Moase and Trasler 1989), Schwann cells (Franz 1990;Grim et al 1992), sympathetic trunk (Auerbach 1954) and the septum of the truncus arteriosus (Franz 1989). Homozygous mutants die on day 14 of gestation presumably because of the malformation of the cardiac outflow tract (Auerbach 1954;Franz 1989).…”