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Notch1 signals through Jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud
Author(s) -
Francis Jeffrey C.,
Radtke Freddy,
Logan Malcolm P.O.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20590
Subject(s) - apical ectodermal ridge , biology , limb bud , limb development , mesenchyme , notch signaling pathway , zone of polarizing activity , microbiology and biotechnology , cell fate determination , ectoderm , fibroblast growth factor , morphogenesis , anatomy , receptor , signal transduction , genetics , mesenchymal stem cell , transcription factor , embryogenesis , embryo , gene
The Notch family of receptors is involved in a wide variety of developmental processes, including cell fate specification, cell proliferation, and cell survival decisions during cell differentiation and tissue morphogenesis. Notch1 and Notch ligands are expressed in the developing limbs, and Notch signalling has been implicated in the formation of a variety of tissues that comprise the limb, such as the skeleton, musculature, and vasculature. Notch signalling has also been implicated in regulating overall limb size. We have used a conditional allele of Notch1 in combination with two different Cre transgenic lines to delete Notch1 function either in the limb mesenchyme or in the apical ectodermal ridge (AER) and limb ectoderm. We demonstrate that Notch signalling, involving Notch1 and Jagged2 , is required to regulate the number of Fgf8 ‐expressing cells that comprise the AER and that regulation of the levels of fibroblast growth factor signalling is important for the freeing of the digits during normal limb formation. Regulation of the extent of the AER is achieved by Notch signalling positively regulating apoptosis in the AER. We also demonstrate that Notch1 is not required for proper formation of all the derivatives of the limb mesenchyme. Developmental Dynamics 234:1006–1015, 2005. © 2005 Wiley‐Liss, Inc.