Notch1 signals through Jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud

TY - JOUR

T1 - Notch1 signals through Jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud

AU - Francis, Jeffrey C

AU - Radtke, Freddy

AU - Logan, Malcolm P O

N1 - Copyright 2005 Wiley-Liss, Inc.

PY - 2005/12

Y1 - 2005/12

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis/genetics

KW - Ectoderm/cytology

KW - Extremities/embryology

KW - Fibroblast Growth Factor 8/metabolism

KW - Fluorescent Antibody Technique

KW - Gene Expression Regulation, Developmental

KW - In Situ Hybridization

KW - In Situ Nick-End Labeling

KW - Jagged-2 Protein

KW - Limb Buds

KW - Membrane Proteins/metabolism

KW - Mice

KW - Mice, Transgenic

KW - Receptor, Notch1/metabolism

KW - Signal Transduction/genetics

U2 - 10.1002/dvdy.20590

DO - 10.1002/dvdy.20590

M3 - Article

C2 - 16245338

SN - 1058-8388

VL - 234

SP - 1006

EP - 1015

JO - Developmental dynamics : an official publication of the American Association of Anatomists

JF - Developmental dynamics : an official publication of the American Association of Anatomists

IS - 4

ER -