Abnormal pyramidal decussation and bilateral projection of the corticospinal tract axons in mice lacking the heparan sulfate endosulfatases, Sulf1 and Sulf2 References: S Aizawa, T Okada et al., Frontiers in Molecular Neuroscience 12, 333, 2020 Contact: Prof. M Masu From Department of Molecular Neurobiology Heparan sulfate (HS) interacts with a wide range of signaling molecules and their rceptors. The endosulfatases, Sulf1 and Sulf2, regulate multiple signaling pathways positively or negatively through desulfation of HS. Here we report anatomical and functional defects of the corticospinal tract (CST) in Sulf1/2 double knockout (DKO) mice. The CST plays an important role in controlling voluntary movement. In the wild-type mice, the CST fibers, originating in the mortor cortex, extend onto the ventral medulla, and the majority of fibers cross the midline at the pyramidal decussation dorsally, then project to the contralateral spinal cord. In the DKO mice, some CST fibers normally cross the midline, whereas others extend ipsilaterally. Consistent with aberrant bilateral projections in the spinal cord, stimulation of 1 side of the motor cortex evokes bilateral responses in the forelimb muscles. Furthermore, the DKO mice perform poorly in skilled reaching and grasping tasks in a single pellet reaching test, indicating that they have impaired motor movements. Single pellet reaching test (%) Wild-type DKO 0 10 20 30 40 slit food pellet rate for successful reach and grasp (arrows) Wild-type Sulf1/2 DKO lateral view ventral view cortex spinal cord lateral view ventral view corticospinal tract (CST) medulla pyramidal decussation spinal cord cortex heparan sulfate proteoglycan core protein heparan sulfate (HS) Sulf1/2 Sulf1/2 Sulf1/2 extracellularly remove specific sulfate groups from HS.

From Department of Molecular Neurobiology...From Department of Molecular Neurobiology Heparan sulfate (HS) interacts with a wide range of signaling molecules and their rceptors. The

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Page 1: From Department of Molecular Neurobiology...From Department of Molecular Neurobiology Heparan sulfate (HS) interacts with a wide range of signaling molecules and their rceptors. The

Abnormal pyramidal decussation and bilateral projection of the corticospinal tract axons in mice lacking the heparan sulfate endosulfatases, Sulf1 and Sulf2

References: S Aizawa, T Okada et al., Frontiers in Molecular Neuroscience 12, 333, 2020 Contact: Prof. M Masu

From Department of Molecular Neurobiology

Heparan sulfate (HS) interacts with a wide range of signaling molecules and their rceptors. The endosulfatases, Sulf1 and Sulf2,regulate multiple signaling pathways positively or negatively through desulfation of HS. Here we report anatomical and functionaldefects of the corticospinal tract (CST) in Sulf1/2 double knockout (DKO) mice. The CST plays an important role in controlling voluntary movement. In the wild-type mice, the CST fibers, originating in the mortor cortex, extend onto the ventral medulla, and the majority of fibers cross the midline at the pyramidal decussation dorsally, then project to the contralateral spinal cord. In the DKO mice, some CST fibers normally cross the midline, whereas others extend ipsilaterally. Consistent with aberrant bilateral projections in the spinal cord, stimulation of 1 side of the motor cortex evokes bilateral responses in the forelimb muscles. Furthermore, the DKO mice perform poorly in skilled reaching and grasping tasks in a single pellet reaching test, indicating that they have impaired motor movements.

Single pellet reaching test

(%)

Wild-type

DKO

0 10 20 30 40

slit

food pellet

rate for successfulreach and grasp (arrows)

Wild-type Sulf1/2 DKOlateral view

ventral view

cortex

spinalcord