Breaking constraint of mammalian axial formulae

Gabriel M. Hauswirth, Victoria C. Garside, Lisa S. F. Wong, Heidi Bildsoe, Jan Manent, Yi-Cheng Chang, Christian M. Nefzger, Jaber Firas, Joseph Chen, Fernando J. Rossello, Jose M. Polo and Edwina McGlinn ()
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Gabriel M. Hauswirth: EMBL Australia, Monash University
Victoria C. Garside: EMBL Australia, Monash University
Lisa S. F. Wong: EMBL Australia, Monash University
Heidi Bildsoe: EMBL Australia, Monash University
Jan Manent: EMBL Australia, Monash University
Yi-Cheng Chang: EMBL Australia, Monash University
Christian M. Nefzger: Australian Regenerative Medicine Institute, Monash University
Jaber Firas: Australian Regenerative Medicine Institute, Monash University
Joseph Chen: Australian Regenerative Medicine Institute, Monash University
Fernando J. Rossello: Australian Regenerative Medicine Institute, Monash University
Jose M. Polo: Australian Regenerative Medicine Institute, Monash University
Edwina McGlinn: EMBL Australia, Monash University

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract The vertebral column of individual mammalian species often exhibits remarkable robustness in the number and identity of vertebral elements that form (known as axial formulae). The genetic mechanism(s) underlying this constraint however remain ill-defined. Here, we reveal the interplay of three regulatory pathways (Gdf11, miR-196 and Retinoic acid) is essential in constraining total vertebral number and regional axial identity in the mouse, from cervical through to tail vertebrae. All three pathways have differing control over Hox cluster expression, with heterochronic and quantitative changes found to parallel changes in axial identity. However, our work reveals an additional role for Hox genes in supporting axial elongation within the tail region, providing important support for an emerging view that mammalian Hox function is not limited to imparting positional identity as the mammalian body plan is laid down. More broadly, this work provides a molecular framework to interrogate mechanisms of evolutionary change and congenital anomalies of the vertebral column.

Date: 2022
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DOI: 10.1038/s41467-021-27335-z

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