Muscle-selective RUNX3 dependence of sensorimotor circuit development
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Muscle-selective RUNX3 dependence of sensorimotor circuit development. / Wang, Yiqiao; Wu, Haohao; Zelenin, Pavel; Fontanet, Paula; Wanderoy, Simone; Petitpré, Charles; Comai, Glenda; Bellardita, Carmelo; Xue-Franzén, Yongtao; Huettl, Rosa Eva; Huber, Andrea B.; Tajbakhsh, Shahragim; Kiehn, Ole; Ernfors, Patrik; Deliagina, Tatiana G.; Lallemend, François; Hadjab, Saida.
In: Development (Cambridge), Vol. 146, No. 20, dev181750, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Muscle-selective RUNX3 dependence of sensorimotor circuit development
AU - Wang, Yiqiao
AU - Wu, Haohao
AU - Zelenin, Pavel
AU - Fontanet, Paula
AU - Wanderoy, Simone
AU - Petitpré, Charles
AU - Comai, Glenda
AU - Bellardita, Carmelo
AU - Xue-Franzén, Yongtao
AU - Huettl, Rosa Eva
AU - Huber, Andrea B.
AU - Tajbakhsh, Shahragim
AU - Kiehn, Ole
AU - Ernfors, Patrik
AU - Deliagina, Tatiana G.
AU - Lallemend, François
AU - Hadjab, Saida
PY - 2019
Y1 - 2019
N2 - The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 also controls the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin 3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator that is crucial for specifying a generic PSN type identity after neurogenesis is later regulated by target muscle-derived signals to contribute to the specialized aspects of the sensorimotor connection selectivity.
AB - The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 also controls the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin 3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator that is crucial for specifying a generic PSN type identity after neurogenesis is later regulated by target muscle-derived signals to contribute to the specialized aspects of the sensorimotor connection selectivity.
KW - Dorsal root ganglia
KW - Neuronal specification
KW - Neurotrophins
KW - Sensorimotor circuit
KW - Sensory system
U2 - 10.1242/dev.181750
DO - 10.1242/dev.181750
M3 - Journal article
C2 - 31575648
AN - SCOPUS:85074118017
VL - 146
JO - Development
JF - Development
SN - 0950-1991
IS - 20
M1 - dev181750
ER -
ID: 231242927