TY - JOUR
T1 - An evolutionarily acquired microRNA shapes development of mammalian cortical projections
AU - Diaz, Jessica L.
AU - Siththanandan, Verl B.
AU - Lu, Victoria
AU - Gonzalez-Nava, Nicole
AU - Pasquina, Lincoln
AU - MacDonald, Jessica L.
AU - Woodworth, Mollie B.
AU - Ozkan, Abdulkadir
AU - Nair, Ramesh
AU - He, Zihuai
AU - Sahni, Vibhu
AU - Sarnow, Peter
AU - Palmer, Theo D.
AU - Macklis, Jeffrey D.
AU - Tharin, Suzanne
N1 - Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/11/17
Y1 - 2020/11/17
N2 - The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are coexpressed across multiple projection neuron subtypes. Here, we discover 17 CSMN-enriched microRNAs (miRNAs), 15 of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is a demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.
AB - The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are coexpressed across multiple projection neuron subtypes. Here, we discover 17 CSMN-enriched microRNAs (miRNAs), 15 of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is a demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.
KW - Cerebral cortex | cortical development | microRNA | motor neuron | projection neuron
UR - http://www.scopus.com/inward/record.url?scp=85096361686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096361686&partnerID=8YFLogxK
U2 - 10.1073/pnas.2006700117
DO - 10.1073/pnas.2006700117
M3 - Article
C2 - 33139574
AN - SCOPUS:85096361686
SN - 0027-8424
VL - 117
SP - 29113
EP - 29122
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 - 46
ER -