An interdigit signalling centre instructs coordinate phalanx-joint formation governed by 5′Hoxd–Gli3 antagonism

Bau-Lin Huang (), Anna Trofka, Aki Furusawa, Jacqueline L. Norrie, Adam H. Rabinowitz, Steven A. Vokes, M. Mark Taketo, Jozsef Zakany and Susan Mackem ()
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Bau-Lin Huang: Cancer and Developmental Biology Laboratory, CCR, NCI
Anna Trofka: Cancer and Developmental Biology Laboratory, CCR, NCI
Aki Furusawa: Cancer and Developmental Biology Laboratory, CCR, NCI
Jacqueline L. Norrie: University of Texas at Austin, Austin, Texas 78712, USA
Adam H. Rabinowitz: University of Texas at Austin, Austin, Texas 78712, USA
Steven A. Vokes: University of Texas at Austin, Austin, Texas 78712, USA
M. Mark Taketo: Graduate School of Medicine, Kyoto University
Jozsef Zakany: University of Geneva
Susan Mackem: Cancer and Developmental Biology Laboratory, CCR, NCI

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract The number of phalanges and joints are key features of digit ‘identity’ and are central to limb functionality and evolutionary adaptation. Prior chick work indicated that digit phalanges and their associated joints arise in a different manner than the more sparsely jointed long bones, and their identity is regulated by differential signalling from adjacent interdigits. Currently, there is no genetic evidence for this model, and the molecular mechanisms governing digit joint specification remain poorly understood. Using genetic approaches in mouse, here we show that functional 5′Hoxd–Gli3 antagonism acts indirectly, through Bmp signalling from the interdigital mesenchyme, to regulate specification of joint progenitors, which arise in conjunction with phalangeal precursors at the digit tip. Phalanx number, although co-regulated, can be uncoupled from joint specification. We propose that 5′Hoxd genes and Gli3 are part of an interdigital signalling centre that sets net Bmp signalling levels from different interdigits to coordinately regulate phalanx and joint formation.

Date: 2016
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DOI: 10.1038/ncomms12903

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