Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin

Javier Capdevila; Tohru Tsukui; Concepción Rodríguez Esteban; Vincenzo Zappavigna; Juan Carlos Izpisúa Belmonte

doi:10.1016/S1097-2765(00)80393-7

Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin

Javier Capdevila, Tohru Tsukui, Concepción Rodríguez Esteban, Vincenzo Zappavigna, Juan Carlos Izpisúa Belmonte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

253 Scopus citations

Abstract

The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth. We also uncover an antagonistic relationship between the secreted factors Gremlin and BMPs required to maintain the Shh/FGF loop that regulates distal outgrowth. These proximal and distal factors have coordinated activities: Meis2 can repress distal genes, and Bmps and Hoxd genes restrict Meis2 expression to the proximal limb bud. Moreover, combinations of BMPs and AER factors are sufficient to distalize proximal limb cells. Our results unveil a novel set of proximal-distal regulatory interactions that establish and maintain outgrowth of the vertebrate limb.

Original language	English (US)
Pages (from-to)	839-849
Number of pages	11
Journal	Molecular cell
Volume	4
Issue number	5
DOIs	https://doi.org/10.1016/S1097-2765(00)80393-7
State	Published - Nov 1999
Externally published	Yes

Bibliographical note

Funding Information:
We apologize for the impossibility of citing all relevant references, due to space constraints. We thank Phil Beachy for providing the Shh −/− mice, Richard Harland for providing the mouse Gremlin probe, Lee Niswander and Cliff Tabin for RCAS constructs, Juan Hurlé, Steve O'Gorman, Licia Selleri, and Miguel Torres for sharing unpublished data, Dirk Büscher and Ana Tavares for insightful discussions, and Lorraine Hooks for help in preparing the manuscript. V. Z. is supported by grants from the Italian Association for Cancer Research (AIRC) and from Telethon. This work was supported by grants from the G. Harold and Leila Y. Mathers Charitable Foundation and the NSF to J. C. I. B., who is a Pew Scholar.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(00)80393-7

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title = "Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin",

abstract = "The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth. We also uncover an antagonistic relationship between the secreted factors Gremlin and BMPs required to maintain the Shh/FGF loop that regulates distal outgrowth. These proximal and distal factors have coordinated activities: Meis2 can repress distal genes, and Bmps and Hoxd genes restrict Meis2 expression to the proximal limb bud. Moreover, combinations of BMPs and AER factors are sufficient to distalize proximal limb cells. Our results unveil a novel set of proximal-distal regulatory interactions that establish and maintain outgrowth of the vertebrate limb.",

author = "Javier Capdevila and Tohru Tsukui and Esteban, {Concepci{\'o}n Rodr{\'i}guez} and Vincenzo Zappavigna and Belmonte, {Juan Carlos Izpis{\'u}a}",

note = "Funding Information: We apologize for the impossibility of citing all relevant references, due to space constraints. We thank Phil Beachy for providing the Shh −/− mice, Richard Harland for providing the mouse Gremlin probe, Lee Niswander and Cliff Tabin for RCAS constructs, Juan Hurl{\'e}, Steve O'Gorman, Licia Selleri, and Miguel Torres for sharing unpublished data, Dirk B{\"u}scher and Ana Tavares for insightful discussions, and Lorraine Hooks for help in preparing the manuscript. V. Z. is supported by grants from the Italian Association for Cancer Research (AIRC) and from Telethon. This work was supported by grants from the G. Harold and Leila Y. Mathers Charitable Foundation and the NSF to J. C. I. B., who is a Pew Scholar. ",

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Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin

Abstract

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