Molecular analysis of regulative events in the developing chick limb

Chris Mahony, Neil Vargesson (Corresponding Author)

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The developing chick limb has the remarkable ability to regulate for the loss of large amounts of mesenchyme and maintain a normal limb pattern in early (Hamburger and Hamilton Stage 19; E3) limbs. How the limb can regulate for tissue loss and why this ability is lost as development proceeds (after Hamburger and Hamilton Stage 21; E3.5) is unclear. We have investigated the origins of cells involved in regulative processes and, for the first time, the molecular changes occurring, and find striking differences between developmental time points just 0.5 days apart. We demonstrate that subtle changes in cell dispersal and cell proliferation occur in HH St21 limbs but not in HH St19 limbs and also demonstrate that there is no net replacement of removed tissue at either HH St21 or St19. We further show that changes in the Fgf8/Shh/Bmp4/Gremlin signaling pathway together with the appearance of distal Hox gene activation coincide with the limbs' ability to regulate for large tissue loss. We also demonstrate that following small tissue loss, limbs can regulate for missing tissue to produce normal pattern with no net replacement of missing tissue, as seen in limbs following large tissue loss. Our results indicate the regulative ability of the limb is not due to changes in cell proliferation, cell lineage nor replacement of the missing tissue – regulative ability is reliant upon the signaling environment remaining.
Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalJournal of Anatomy
Volume223
Issue number1
Early online date16 May 2013
DOIs
Publication statusPublished - 1 Jul 2013

Fingerprint

molecular analysis
limbs (animal)
limb
Extremities
chicks
hamburgers
replacement
cell proliferation
Cell Proliferation
gene activation
tissues
tissue
Homeobox Genes
Cell Lineage
Mesoderm
cells
Transcriptional Activation
loss
gene

Keywords

  • cell proliferation
  • fatemaps
  • mesenchyme removal
  • phocomelia
  • proximo-distal axis
  • thalidomide
  • Bmp4
  • Fgf8
  • gremlin
  • Hox

Cite this

Molecular analysis of regulative events in the developing chick limb. / Mahony, Chris; Vargesson, Neil (Corresponding Author).

In: Journal of Anatomy, Vol. 223, No. 1, 01.07.2013, p. 1-13.

Research output: Contribution to journalArticle

@article{bf9531be806042a4a2f8c95ac8048432,
title = "Molecular analysis of regulative events in the developing chick limb",
abstract = "The developing chick limb has the remarkable ability to regulate for the loss of large amounts of mesenchyme and maintain a normal limb pattern in early (Hamburger and Hamilton Stage 19; E3) limbs. How the limb can regulate for tissue loss and why this ability is lost as development proceeds (after Hamburger and Hamilton Stage 21; E3.5) is unclear. We have investigated the origins of cells involved in regulative processes and, for the first time, the molecular changes occurring, and find striking differences between developmental time points just 0.5 days apart. We demonstrate that subtle changes in cell dispersal and cell proliferation occur in HH St21 limbs but not in HH St19 limbs and also demonstrate that there is no net replacement of removed tissue at either HH St21 or St19. We further show that changes in the Fgf8/Shh/Bmp4/Gremlin signaling pathway together with the appearance of distal Hox gene activation coincide with the limbs' ability to regulate for large tissue loss. We also demonstrate that following small tissue loss, limbs can regulate for missing tissue to produce normal pattern with no net replacement of missing tissue, as seen in limbs following large tissue loss. Our results indicate the regulative ability of the limb is not due to changes in cell proliferation, cell lineage nor replacement of the missing tissue – regulative ability is reliant upon the signaling environment remaining.",
keywords = "cell proliferation, fatemaps, mesenchyme removal, phocomelia, proximo-distal axis, thalidomide, Bmp4, Fgf8, gremlin, Hox",
author = "Chris Mahony and Neil Vargesson",
year = "2013",
month = "7",
day = "1",
doi = "10.1111/joa.12060",
language = "English",
volume = "223",
pages = "1--13",
journal = "Journal of Anatomy",
issn = "0021-8782",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Molecular analysis of regulative events in the developing chick limb

AU - Mahony, Chris

AU - Vargesson, Neil

PY - 2013/7/1

Y1 - 2013/7/1

N2 - The developing chick limb has the remarkable ability to regulate for the loss of large amounts of mesenchyme and maintain a normal limb pattern in early (Hamburger and Hamilton Stage 19; E3) limbs. How the limb can regulate for tissue loss and why this ability is lost as development proceeds (after Hamburger and Hamilton Stage 21; E3.5) is unclear. We have investigated the origins of cells involved in regulative processes and, for the first time, the molecular changes occurring, and find striking differences between developmental time points just 0.5 days apart. We demonstrate that subtle changes in cell dispersal and cell proliferation occur in HH St21 limbs but not in HH St19 limbs and also demonstrate that there is no net replacement of removed tissue at either HH St21 or St19. We further show that changes in the Fgf8/Shh/Bmp4/Gremlin signaling pathway together with the appearance of distal Hox gene activation coincide with the limbs' ability to regulate for large tissue loss. We also demonstrate that following small tissue loss, limbs can regulate for missing tissue to produce normal pattern with no net replacement of missing tissue, as seen in limbs following large tissue loss. Our results indicate the regulative ability of the limb is not due to changes in cell proliferation, cell lineage nor replacement of the missing tissue – regulative ability is reliant upon the signaling environment remaining.

AB - The developing chick limb has the remarkable ability to regulate for the loss of large amounts of mesenchyme and maintain a normal limb pattern in early (Hamburger and Hamilton Stage 19; E3) limbs. How the limb can regulate for tissue loss and why this ability is lost as development proceeds (after Hamburger and Hamilton Stage 21; E3.5) is unclear. We have investigated the origins of cells involved in regulative processes and, for the first time, the molecular changes occurring, and find striking differences between developmental time points just 0.5 days apart. We demonstrate that subtle changes in cell dispersal and cell proliferation occur in HH St21 limbs but not in HH St19 limbs and also demonstrate that there is no net replacement of removed tissue at either HH St21 or St19. We further show that changes in the Fgf8/Shh/Bmp4/Gremlin signaling pathway together with the appearance of distal Hox gene activation coincide with the limbs' ability to regulate for large tissue loss. We also demonstrate that following small tissue loss, limbs can regulate for missing tissue to produce normal pattern with no net replacement of missing tissue, as seen in limbs following large tissue loss. Our results indicate the regulative ability of the limb is not due to changes in cell proliferation, cell lineage nor replacement of the missing tissue – regulative ability is reliant upon the signaling environment remaining.

KW - cell proliferation

KW - fatemaps

KW - mesenchyme removal

KW - phocomelia

KW - proximo-distal axis

KW - thalidomide

KW - Bmp4

KW - Fgf8

KW - gremlin

KW - Hox

U2 - 10.1111/joa.12060

DO - 10.1111/joa.12060

M3 - Article

VL - 223

SP - 1

EP - 13

JO - Journal of Anatomy

JF - Journal of Anatomy

SN - 0021-8782

IS - 1

ER -