PMID- 20531940
OWN - NLM
STAT- MEDLINE
DCOM- 20100907
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 5
DP  - 2010 May 28
TI  - Bare bones pattern formation: a core regulatory network in varying geometries 
      reproduces major features of vertebrate limb development and evolution.
PG  - e10892
LID - 10.1371/journal.pone.0010892 [doi]
LID - e10892
AB  - BACKGROUND: Major unresolved questions regarding vertebrate limb development 
      concern how the numbers of skeletal elements along the proximodistal (P-D) and 
      anteroposterior (A-P) axes are determined and how the shape of a growing limb 
      affects skeletal element formation. There is currently no generally accepted 
      model for these patterning processes, but recent work on cartilage development 
      (chondrogenesis) indicates that precartilage tissue self-organizes into nodular 
      patterns by cell-molecular circuitry with local auto-activating and lateral 
      inhibitory (LALI) properties. This process is played out in the developing limb 
      in the context of a gradient of fibroblast growth factor (FGF) emanating from the 
      apical ectodermal ridge (AER). RESULTS: We have simulated the behavior of the 
      core chondrogenic mechanism of the developing limb in the presence of an FGF 
      gradient using a novel computational environment that permits simulation of LALI 
      systems in domains of varying shape and size. The model predicts the normal 
      proximodistal pattern of skeletogenesis as well as distal truncations resulting 
      from AER removal. Modifications of the model's parameters corresponding to 
      plausible effects of Hox proteins and formins, and of the reshaping of the model 
      limb, bud yielded simulated phenotypes resembling mutational and experimental 
      variants of the limb. Hypothetical developmental scenarios reproduce skeletal 
      morphologies with features of fossil limbs. CONCLUSIONS: The limb chondrogenic 
      regulatory system operating in the presence of a gradient has an inherent, robust 
      propensity to form limb-like skeletal structures. The bare bones framework can 
      accommodate ancillary gene regulatory networks controlling limb bud shaping and 
      establishment of Hox expression domains. This mechanism accounts for major 
      features of the normal limb pattern and, under variant geometries and different 
      parameter values, those of experimentally manipulated, genetically aberrant and 
      evolutionary early forms, with no requirement for an independent system of 
      positional information.
FAU - Zhu, Jianfeng
AU  - Zhu J
AD  - Department of Mathematics, University of Notre Dame, Notre Dame, Indiana, United 
      States of America.
FAU - Zhang, Yong-Tao
AU  - Zhang YT
FAU - Alber, Mark S
AU  - Alber MS
FAU - Newman, Stuart A
AU  - Newman SA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100528
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - *Biological Evolution
MH  - *Body Patterning
MH  - Bone and Bones/*anatomy & histology/*embryology
MH  - Chickens
MH  - Computer Simulation
MH  - Ectoderm/embryology
MH  - Extremities/*embryology
MH  - Fossils
MH  - *Gene Regulatory Networks
MH  - Kinetics
MH  - Limb Buds/embryology
MH  - Models, Biological
MH  - Vertebrates/*embryology
MH  - Wings, Animal/embryology
PMC - PMC2878345
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/06/10 06:00
MHDA- 2010/09/08 06:00
PMCR- 2010/05/28
CRDT- 2010/06/10 06:00
PHST- 2010/03/04 00:00 [received]
PHST- 2010/05/07 00:00 [accepted]
PHST- 2010/06/10 06:00 [entrez]
PHST- 2010/06/10 06:00 [pubmed]
PHST- 2010/09/08 06:00 [medline]
PHST- 2010/05/28 00:00 [pmc-release]
AID - 10-PONE-RA-16776R2 [pii]
AID - 10.1371/journal.pone.0010892 [doi]
PST - epublish
SO  - PLoS One. 2010 May 28;5(5):e10892. doi: 10.1371/journal.pone.0010892.