Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity

Myungin Baek, Vilas Menon, Thomas Jessell, Adam Hantman, Jeremy Dasen

Preprint posted on 9 January 2019

Article now published in Cell Reports at

What cultivates the diversity of spinocerebellar tract neurons? Transcriptomic and genetic study suggests Hox genes to be the key.

Selected by Yen-Chung Chen

Background and context

Coordination of motions depends on communication between the peripheral sensory system and the central nervous system, and spinocerebellar tract neurons are central to this communication. Spinocerebellar tract neurons relay proprioceptive sensory information about muscle tension and position from the body to the cerebellum. When this communication is defective, although motions are maintained, the ability to predict and correct errors is damaged.

Previous retrograde tracing studies have shown that different subpopulations of spinocerebellar tract neurons exist along the rostrocaudal axis, which receive inputs from specific muscle groups that are often functionally antagonistic. This observation leads to the hypothesis that spinocerebellar tract neurons might integrate the information from each muscle pair and transmit the information to the cerebellum for further processing.

While the anatomy and connectivity of spinocerebellar tract neurons have been described, the underlying molecular basis of their diversity and connectivity remains largely unknown. Understanding how spinocerebellar tract neurons are specified and form synapses with different subsets of peripheral sensory neurons could tell us more about how neurons find the right target in a distant and crowded neural nucleus or column and form synapses with the right partner. Furthermore, identification of critical developmental genes may provide a more precise way to manipulate spinocerebellar tract neurons to reveal their role in the motor circuit.

Key findings

In this study, Baek et al. first systematically characterized the anatomy of spinocerebellar tract neurons projecting to the cerebellum by retrograde labeling, identifying eight spatially distinct subpopulations, and then profiled the transcriptomic difference between cervical and thoracic spinocerebellar tract neurons. Transcriptomic analysis revealed differences in the expression of ion channels, neurotransmitter transporters, and transcription factors, suggesting that the spinocerebellar tract neurons in different segments obtain distinct transcriptional programs. The segmental difference is consistent with the early morphogen patterning along the rostrocaudal axis and reminiscent of subtype specification of spinal motor neurons. To better characterize the heterogeneity of spinocerebellar tract neurons within each segment, the authors performed single cell RNA-seq and identified eight transcriptomically distinct clusters, among which one novel subtype, marked by Shox2, Scip, and Fam19A4, was examined in vivo and detected as a subpopulation in the caudal cervical segment.

The authors then asked how these molecularly distinct subtypes of spinocerebellar tract neurons are specified. Inspired by the prominent segmental difference, the authors hypothesized that Hox genes might be the key regulators of neuronal subtype determination, similar to the case of spinal motor neurons and interneurons [1][2]. Indeed, different spinocerebellar tract neurons express a distinct combination of Hox genes. With the loss of function of Hoxc9, a critical regulator of thoracic segment for motor and interneurons, Clarke’s column, a subpopulation of spinocerebellar tract neurons, failed to form in the thoracic segment. On the other hand, the other remaining spinocerebellar tract neurons in the thoracic segment stopped expressing their marker genes and started to express a combination similar to caudal cervical spinocerebellar tract neurons (Figure 1). Regarding circuit formation, thoracic spinocerebellar tract neurons received peripheral sensory innervations that are otherwise exclusive for cervical neurons in the lack of Hoxc9. The changes in gene expression and connectivity upon Hoxc9 loss of function are consistent with a conversion of cell identity from thoracic to cervical spinocerebellar tract neurons.

Figure 1. Spinocerebellar tract neurons within different rostrocaudal segments differ in spatial organization and molecular signature, which is regulated by the expression of Hox genes.


In short, Baek et al. systematically characterized spinocerebellar tract neurons with a transcriptomic approach and identified segmentally distinct subtypes that are governed by Hox gene expression.

Why I like this preprint

Hox genes are critical for spinal motor neurons to further specify into different subpopulations and achieve precise connection with individual muscle groups. Recently, a similar paradigm has been shown to be adopted by some spinal interneurons, making it tempting to speculate that Hox genes are the general hub to integrate information from different morphogen gradients and to define the neural diversity in the spinal cord. If that is the case, how the seemingly ubiquitous expression of Hox genes within a segment can specify different neural types becomes an intriguing question, and this question might be answered by interrogating the crosstalk between cell type-specifying transcription factors and Hox genes. In this preprint, Baek et al. elegantly depicted how the spatial and molecular identities of spinocerebellar tract neurons are governed by Hox genes, demonstrating that Hox regulation is indeed a shared regulatory feature within the spinal cord. Additionally, the characterization of spinocerebellar tract neurons provides a novel context for future study of how fate specifying programs and Hox genes synergistically give rise to neural diversity.

Open question

  1. The spatial distribution of spinocerebellar tract neurons differs segmentally on both ventrodorsal and mediolateral axis, do they come from the same progenitor zone? If not, can single cell RNA-seq give us a hint about which layers spinocerebellar tract neurons come from?
  2. In contrast to spinal motor neurons [3] and V1 interneurons [2], where no prominent change in neuron number was reported with Hoxc9 loss of function, the decrease of thoracic spinocerebellar tract number is intriguing. Is the cell number change as prominent before developmental programmed cell death as it is postnatally? Or alternatively, do thoracic spinocerebellar tract neurons switch to other fates in the absence of Hoxc9?


  1. Dasen, J. S. & Jessell, T. M. Chapter Six Hox Networks and the Origins of Motor Neuron Diversity. Current Topics in Developmental Biology 88, (Elsevier Inc., 2009).
  2. Sweeney, L. B. et al. Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron 97, 341–355.e3 (2018).
  3. Dasen, J. S., Liu, J. P. & Jessell, T. M. Motor neuron columnar fate imposed by sequential phases of Hox-c activity. Nature 425, 926–933 (2003).

Tags: scrna-seq

Posted on: 8 April 2019 , updated on: 11 April 2019


Read preprint (No Ratings Yet)

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the developmental biology category:

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)


List by Nándor Lipták


The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!


List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.


List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020


List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.


List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020


List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020


List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.


List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.


List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.


List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)


List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.


List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019


List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.


List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.


List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London


List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.


List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019


List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.


List by Shikha Nayar

Also in the genetics category:

Semmelweis Symposium 2022: 40th anniversary of international medical education at Semmelweis University

This preList contains preprints discussed during the 'Semmelweis Symposium 2022' (7-9 November), organised around the 40th anniversary of international medical education at Semmelweis University covering a wide range of topics.


List by Nándor Lipták

20th “Genetics Workshops in Hungary”, Szeged (25th, September)

In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link:


List by Nándor Lipták

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)


List by Nándor Lipták

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020


List by Jesus Victorino

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20


List by Maiko Kitaoka et al.

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome


List by Hiral Shah


Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.


List by Sandra Malmgren Hill