Temporal controls over inter-areal cortical projection neuron fate diversity

Nature ◽  
2021 ◽  
Author(s):  
Esther Klingler ◽  
Ugo Tomasello ◽  
Julien Prados ◽  
Justus M. Kebschull ◽  
Alessandro Contestabile ◽  
...  
Keyword(s):  
Projection Neuron ◽  
Cortical Projection ◽  
Cortical Projection Neuron

scholarly journals Lmo4 and Clim1 Progressively Delineate Cortical Projection Neuron Subtypes during Development

2009 ◽  
Vol 19 (suppl_1) ◽  
pp. i62-i69 ◽  
Author(s):  
Eiman Azim ◽  
Sara J. Shnider ◽  
Gustav Y. Cederquist ◽  
U. Shivraj Sohur ◽  
Jeffrey D. Macklis
Keyword(s):  
Projection Neuron ◽  
Cortical Projection ◽  
Cortical Projection Neuron

scholarly journals An evolutionarily acquired microRNA shapes development of mammalian cortical projections

2020 ◽  
Author(s):  
Jessica L Diaz ◽  
Verl B Siththanandan ◽  
Victoria Lu ◽  
Nicole Gonzalez-Nava ◽  
Lincoln Pasquina ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Cognitive Skills ◽  
Corticospinal Tract ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Complex Motor ◽  
Callosal Projection ◽  
Cortical Projection Neuron

AbstractThe 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 co-expressed across multiple projection neuron subtypes. Here, we discover seventeen CSMN-enriched microRNAs (miRNAs), fifteen 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 the first 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.Significance StatementThe mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills, including the corticospinal tract and corpus callosum. The neurons giving rise to these projections - corticospinal and callosal projection neurons - develop from the same progenitors, but acquire strikingly different fates. The broad evolutionary conservation of known genes controlling cortical projection neuron fates raises the question of how the more narrowly conserved corticospinal and callosal projections evolved. We identify a microRNA cluster selectively expressed by corticospinal projection neurons and exclusive to placental mammals. One of these microRNAs promotes corticospinal fate via regulation of the callosal gene LMO4, suggesting a mechanism whereby microRNA regulation during development promotes evolution of neuronal diversity.

scholarly journals Basic Helix-Loop-Helix Transcription Factors Cooperate To Specify a Cortical Projection Neuron Identity

2007 ◽  
Vol 28 (5) ◽  
pp. 1456-1469 ◽  
Author(s):  
Pierre Mattar ◽  
Lisa Marie Langevin ◽  
Kathryn Markham ◽  
Natalia Klenin ◽  
Salma Shivji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Projection Neuron ◽  
Luciferase Assay ◽  
Bhlh Gene ◽  
Cortical Projection ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Cortical Projection Neuron

ABSTRACT Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h). We identify the bHLH gene Math3 as a dorsally restricted Ngn2 transcriptional target and cofactor, which synergizes with Ngn2 to accelerate target gene transcription in the cortex. Using a novel in vivo luciferase assay, we show that Ngn2 generates only ∼60% of the transcriptional drive in ventral versus dorsal telencephalic domains, an activity that is augmented by Math3, providing a mechanistic basis for regional differences in Ngn2 function. Cortical bHLH genes thus cooperate to control transcriptional strength, thereby temporally coordinating downstream gene expression.

scholarly journals Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

2015 ◽  
Vol 112 (37) ◽  
pp. 11702-11707 ◽  
Author(s):  
William L. McKenna ◽  
Christian F. Ortiz-Londono ◽  
Thomas K. Mathew ◽  
Kendy Hoang ◽  
Sol Katzman ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Projection Neuron ◽  
Dependent Manner ◽  
Neuron Development ◽  
Cortical Projection ◽  
Expression Of Genes ◽  
Axon Development ◽  
Mutual Regulation ◽  
A Cell ◽  
Cortical Projection Neuron

Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.

scholarly journals Ranbp1, Deleted in DiGeorge/22q11.2 Deletion Syndrome, is a Microcephaly Gene That Selectively Disrupts Layer 2/3 Cortical Projection Neuron Generation

2014 ◽  
Vol 25 (10) ◽  
pp. 3977-3993 ◽  
Author(s):  
Elizabeth M. Paronett ◽  
Daniel W. Meechan ◽  
Beverly A. Karpinski ◽  
Anthony-Samuel LaMantia ◽  
Thomas M. Maynard
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Projection Neuron ◽  
Deletion Syndrome ◽  
Cortical Projection ◽  
22Q11.2 Deletion ◽  
Layer 2 ◽  
Cortical Projection Neuron

scholarly journals A microfluidic device to investigate axon targeting by limited numbers of purified cortical projection neuron subtypes

2012 ◽  
Vol 4 (11) ◽  
pp. 1398 ◽  
Author(s):  
Suzanne Tharin ◽  
Chandrasekhar R. Kothapalli ◽  
Pembe Hande Ozdinler ◽  
Lincoln Pasquina ◽  
Seok Chung ◽  
...  
Keyword(s):  
Microfluidic Device ◽  
Projection Neuron ◽  
Cortical Projection ◽  
Axon Targeting ◽  
Cortical Projection Neuron
Sign in / Sign up

Export Citation Format

Share Document