TY - JOUR
T1 - Critical roles of ARHGAP36 as a signal transduction mediator of shh pathway in lateral motor columnar specification
AU - Nam, Heejin
AU - Jeon, Shin
AU - An, Hyejin
AU - Yoo, Jaeyoung
AU - Lee, Hyo Jong
AU - Lee, Soo Kyung
AU - Lee, Seunghee
N1 - Funding Information:
We thank Dr. Jae W Lee (OHSU, Portland, USA) for reagents and many helpful suggestions during the course of this work as well as for critically reading the manuscript. This research was supported by grants of the Korea Health Technology R and D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI17C0447) to S Lee and NIH/NINDS (R01NS100471) to S-KL.
Publisher Copyright:
© Nam et al.
PY - 2019/7
Y1 - 2019/7
N2 - During spinal cord development, Sonic hedgehog (Shh), secreted from the floor plate, plays an important role in the production of motor neurons by patterning the ventral neural tube, which establishes MN progenitor identity. It remains unknown, however, if Shh signaling plays a role in generating columnar diversity of MNs that connect distinct target muscles. Here, we report that Shh, expressed in MNs, is essential for the formation of lateral motor column (LMC) neurons in vertebrate spinal cord. This novel activity of Shh is mediated by its downstream effector ARHGAP36, whose expression is directly induced by the MN-specific transcription factor complex Isl1-Lhx3. Furthermore, we found that AKT stimulates the Shh activity to induce LMC MNs through the stabilization of ARHGAP36 proteins. Taken together, our data reveal that Shh, secreted from MNs, plays a crucial role in generating MN diversity via a regulatory axis of Shh-AKTARHGAP36 in the developing mouse spinal cord.
AB - During spinal cord development, Sonic hedgehog (Shh), secreted from the floor plate, plays an important role in the production of motor neurons by patterning the ventral neural tube, which establishes MN progenitor identity. It remains unknown, however, if Shh signaling plays a role in generating columnar diversity of MNs that connect distinct target muscles. Here, we report that Shh, expressed in MNs, is essential for the formation of lateral motor column (LMC) neurons in vertebrate spinal cord. This novel activity of Shh is mediated by its downstream effector ARHGAP36, whose expression is directly induced by the MN-specific transcription factor complex Isl1-Lhx3. Furthermore, we found that AKT stimulates the Shh activity to induce LMC MNs through the stabilization of ARHGAP36 proteins. Taken together, our data reveal that Shh, secreted from MNs, plays a crucial role in generating MN diversity via a regulatory axis of Shh-AKTARHGAP36 in the developing mouse spinal cord.
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U2 - 10.7554/eLife.46683
DO - 10.7554/eLife.46683
M3 - Article
C2 - 31305241
AN - SCOPUS:85070659304
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e46683
ER -