Molecular programs guiding arealization of descending cortical pathways
METADATA ONLY
Loading...
Author / Producer
Date
2024-10-17
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
METADATA ONLY
Data
Rights / License
Abstract
Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets1–6. Two cardinal subtypes exist7,8: (1) Slco2a1-expressing neurons (ETdist), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ETprox), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ETdist and ETprox emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis9–12. Here, using cross-areal mapping of axonal projections in the mouse neocortex, we identify the subtype-specific developmental dynamics of ET neurons. Whereas subsets of ETprox emerge by pruning of ETdist axons, others emerge de novo. We outline corresponding subtype-specific developmental transcriptional programs using single-nucleus sequencing. Leveraging these findings, we use postnatal in vivo knockdown of subtype-specific transcription factors to reprogram ET neuron connectivity towards more proximal targets. Together, these results show the functional transcriptional programs driving ET neuron diversity and uncover cell subtype-specific gene regulatory networks that can be manipulated to direct target specificity in motor corticofugal pathways.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
634 (8034)
Pages / Article No.
644 - 651
Publisher
Nature
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Cell type diversity; Neuronal development
Organisational unit
09580 - Platt, Randall / Platt, Randall
Notes
Funding
175830 - Identification of convergent molecular pathways in autism spectrum disorder by in utero genome editing and transcriptional profiling of cortical projection neuron subtypes (SNF)
205965 - Dynamic consortium interactions that establish the microbiota during (SNF)
211573 - SNF 211573 Bridge / Platt (SNF)
ETH-27 18-2 - In vivo interrogation of cellular essential genes with CRISPR-Cas9 (ETHZ)
851021 - Reconstructing cellular histories with transcriptional recording (EC)
175830 - Identification of convergent molecular pathways in autism spectrum disorder by in utero genome editing and transcriptional profiling of cortical projection neuron subtypes (SNF)
205965 - Dynamic consortium interactions that establish the microbiota during (SNF)
211573 - SNF 211573 Bridge / Platt (SNF)
ETH-27 18-2 - In vivo interrogation of cellular essential genes with CRISPR-Cas9 (ETHZ)
851021 - Reconstructing cellular histories with transcriptional recording (EC)
175830 - Identification of convergent molecular pathways in autism spectrum disorder by in utero genome editing and transcriptional profiling of cortical projection neuron subtypes (SNF)