期刊
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
卷 54, 期 1, 页码 125-134出版社
UNIV BASQUE COUNTRY UPV-EHU PRESS
DOI: 10.1387/ijdb.082783sr
关键词
retinoic acid; myogenesis; tendon; limb bud; chick
资金
- BBSRC
- MYORES
- BBSRC [BB/D521865/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D521865/1] Funding Source: researchfish
Retinoic acid (RA) plays an essential role in the development of many embryonic tissues, including the developing tetrapod limb bud. At early stages of limb development, RA levels are highest proximally and regulate the migration of myoblasts into the limb. As the premyogenic progenitor cells migrate into the limb and accumulate in premuscle masses, they express Pax3 and Meox2. Myogenic differentiation is initiated by expression of Myf5 and MyoD, and both Pax3 and Meox2 are required for normal Myf5 expression. We show by loss of function using the inhibitor citral, that RA signalling within the limb bud is required to maintain Pax3 and Meox2 in the progenitor and Myf5 and MyoD in the differentiating myoblasts. Treatment with excess RA showed a differential effect: Meox2 and Pax3 showed localised down-regulation of expression in the limb. In contrast, there was a dramatic down-regulation of expression of MyoD, Myf5 and Meox1. The down-regulation of myogenic gene expression in response to inhibition of RA signalling, and differential response to application of excess RA, in the absence of changes to cell proliferation and apoptosis, indicate that myogenic specification and differentiation in the developing limb possess a complex sensitivity to RA concentrations.
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