Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes.

Mercader Huber, Nadia; Leonardo, E; Piedra, M E; Martínez-A, C; Ros, M A; Torres, M (2000). Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes. Development, 127(18), pp. 3961-3970. Company of Biologists Limited

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Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Mercader Huber, Nadia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0950-1991

Publisher:

Company of Biologists Limited

Language:

English

Submitter:

Nadia Isabel Mercader Huber

Date Deposited:

30 Jun 2016 16:37

Last Modified:

30 Jun 2016 16:37

PubMed ID:

10952894

BORIS DOI:

10.7892/boris.79628

URI:

https://boris.unibe.ch/id/eprint/79628

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