HOX gene expression in the developing human spine

John E. G. Lawrence, Kenny Roberts, Elizabeth Tuck, Tong Li, Lira Mamanova, Petra Balogh, Inga Usher, Alice Piapi, Pavel Mazin, Nathaniel D. Anderson, Liam Bolt, Laura Richardson, Elena Prigmore, Xiaoling He, Roger A. Barker, Adrienne Flanagan, Matthew D. Young, Sarah A. Teichmann, Omer Bayraktar () and Sam Behjati ()
Additional contact information
John E. G. Lawrence: Wellcome Genome Campus
Kenny Roberts: Wellcome Genome Campus
Elizabeth Tuck: Wellcome Genome Campus
Tong Li: Wellcome Genome Campus
Lira Mamanova: Wellcome Genome Campus
Petra Balogh: Royal National Orthopaedic Hospital
Inga Usher: University College London Great Ormond Street Institute of Child Health
Alice Piapi: University College London Great Ormond Street Institute of Child Health
Pavel Mazin: Wellcome Genome Campus
Nathaniel D. Anderson: Wellcome Genome Campus
Liam Bolt: Wellcome Genome Campus
Laura Richardson: Wellcome Genome Campus
Elena Prigmore: Wellcome Genome Campus
Xiaoling He: University of Cambridge
Roger A. Barker: University of Cambridge
Adrienne Flanagan: Department of Pathology, University College London (UCL) Cancer Institute
Matthew D. Young: Wellcome Genome Campus
Sarah A. Teichmann: Wellcome Genome Campus
Omer Bayraktar: Wellcome Genome Campus
Sam Behjati: Wellcome Genome Campus

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Positional coding along the anterior-posterior axis is regulated by HOX genes, whose 3’ to 5’ expression correlates with location along this axis. The precise utilisation of HOX genes in different human cell types is not fully understood. Here, we use single-cell and spatial-transcriptomics, along with in-situ sequencing, to create a developmental atlas of the human fetal spine. We analyse HOX gene expression across cell types during development, finding that neural-crest derivatives unexpectedly retain the anatomical HOX code of their origin while also adopting the code of their destination. This trend is confirmed across multiple organs. In the axial plane of the spinal cord, we find distinct patterns in the ventral and dorsal domains, providing insights into motor pool organisation and loss of collinearity in HOXB genes. Our findings shed new light on HOX gene expression in the developing spine, highlighting a HOX gene ‘source code’ in neural-crest cell derivatives.

Date: 2024
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DOI: 10.1038/s41467-024-54187-0

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