Tbx4 function during hindlimb development reveals a novel mechanism to explain the origins of proximal limb defects

Veronique Duboc; Fatima A Sulaiman; Eleanor Feneck; Anna Kucharska; Donald Bell; Muriel Holder-Espinasse; Malcolm Logan

Tbx4 function during hindlimb development reveals a novel mechanism to explain the origins of proximal limb defects

Veronique Duboc, Fatima A Sulaiman, Eleanor Feneck, Anna Kucharska, Donald Bell, Muriel Holder-Espinasse, Malcolm Logan

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Abstract

We dissect genetically a gene regulatory network, including the transcription factors Tbx4, Pitx1 and Isl1 that act cooperatively to establish the hindlimb bud and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects in the Tbx4 mutant result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing a novel explanation for the origins of proximally-biased limb defects.

Original language	English
Journal	Development
Publication status	Published - 2 Aug 2021

Keywords

Congenital limb abnormalities,
Pitx1
Tbx4,
limb formation,
Chondrogenesis,

Access to Document

dev199580Accepted author manuscript, 3.46 MBLicence: CC BY

Cite this

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title = "Tbx4 function during hindlimb development reveals a novel mechanism to explain the origins of proximal limb defects",

abstract = "We dissect genetically a gene regulatory network, including the transcription factors Tbx4, Pitx1 and Isl1 that act cooperatively to establish the hindlimb bud and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects in the Tbx4 mutant result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing a novel explanation for the origins of proximally-biased limb defects.",

keywords = "Congenital limb abnormalities,, Pitx1, Tbx4,, limb formation,, Chondrogenesis,",

author = "Veronique Duboc and Sulaiman, {Fatima A} and Eleanor Feneck and Anna Kucharska and Donald Bell and Muriel Holder-Espinasse and Malcolm Logan",

year = "2021",

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language = "English",

journal = "Development",

issn = "0950-1991",

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TY - JOUR

T1 - Tbx4 function during hindlimb development reveals a novel mechanism to explain the origins of proximal limb defects

AU - Duboc, Veronique

AU - Sulaiman, Fatima A

AU - Feneck, Eleanor

AU - Kucharska, Anna

AU - Bell, Donald

AU - Holder-Espinasse, Muriel

AU - Logan, Malcolm

PY - 2021/8/2

Y1 - 2021/8/2

N2 - We dissect genetically a gene regulatory network, including the transcription factors Tbx4, Pitx1 and Isl1 that act cooperatively to establish the hindlimb bud and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects in the Tbx4 mutant result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing a novel explanation for the origins of proximally-biased limb defects.

AB - We dissect genetically a gene regulatory network, including the transcription factors Tbx4, Pitx1 and Isl1 that act cooperatively to establish the hindlimb bud and identify key differences in the pathways that initiate formation of the hindlimb and forelimb. Using live image analysis of limb mesenchyme cells undergoing chondrogenesis in micromass culture, we distinguish a series of changes in cellular behaviours and cohesiveness that are required for chondrogenic precursors to undergo differentiation. Furthermore, we provide evidence that the proximal hindlimb defects in the Tbx4 mutant result from a failure in the early differentiation step of chondroprogenitors into chondrocytes, providing a novel explanation for the origins of proximally-biased limb defects.

KW - Congenital limb abnormalities,

KW - Pitx1

KW - Tbx4,

KW - limb formation,

KW - Chondrogenesis,

M3 - Article

SN - 0950-1991

JO - Development

JF - Development

ER -