TY - JOUR
T1 - BARHL2 transcription factor regulates the ipsilateral/ contralateral subtype divergence in postmitotic dI1 neurons of the developing spinal cord
AU - Ding, Qian
AU - Joshi, Pushkar S.
AU - Xie, Zheng Hua
AU - Xiang, Mengqing
AU - Gan, Lin
PY - 2012/1/31
Y1 - 2012/1/31
N2 - In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.
AB - In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.
KW - Atoh1/Math1
KW - BarH/BarH-like
KW - Neurogenesis
KW - Neuronal differentiation
KW - Robo3/Rig1
UR - http://www.scopus.com/inward/record.url?scp=84857130451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857130451&partnerID=8YFLogxK
U2 - 10.1073/pnas.1112392109
DO - 10.1073/pnas.1112392109
M3 - Article
C2 - 22307612
AN - SCOPUS:84857130451
SN - 0027-8424
VL - 109
SP - 1566
EP - 1571
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -