PMID- 25217052
OWN - NLM
STAT- MEDLINE
DCOM- 20150707
LR  - 20211021
IS  - 1943-2631 (Electronic)
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 198
IP  - 3
DP  - 2014 Nov
TI  - Genetic interactions between Shox2 and Hox genes during the regional growth and 
      development of the mouse limb.
PG  - 1117-26
LID - 10.1534/genetics.114.167460 [doi]
AB  - The growth and development of the vertebrate limb relies on homeobox genes of the 
      Hox and Shox families, with their independent mutation often giving 
      dose-dependent effects. Here we investigate whether Shox2 and Hox genes function 
      together during mouse limb development by modulating their relative dosage and 
      examining the limb for nonadditive effects on growth. Using double mRNA 
      fluorescence in situ hybridization (FISH) in single embryos, we first show that 
      Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 
      expression restricted to the proximal limb along with Hoxd9 and Hoxa11 
      expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating 
      mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D 
      cluster deletions, we then show that their coordinated proximal limb expression 
      is critical to generate normally proportioned limb segments. These epistatic 
      interactions tune limb length, where Shox2 underexpression enhances, and Shox2 
      overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or 
      Hox genes leads to a similar reduction in Runx2 expression in the developing 
      humerus, suggesting their concerted action drives cartilage maturation during 
      normal development. While we furthermore provide evidence that Hox gene function 
      influences Shox2 expression, this regulation is limited in extent and is unlikely 
      on its own to be a major explanation for their genetic interaction. Given the 
      similar effect of human SHOX mutations on regional limb growth, Shox and Hox 
      genes may generally function as genetic interaction partners during the growth 
      and development of the proximal vertebrate limb.
CI  - Copyright (c) 2014 by the Genetics Society of America.
FAU - Neufeld, Stanley J
AU  - Neufeld SJ
AD  - Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 
      1N4, Canada.
FAU - Wang, Fan
AU  - Wang F
AD  - Department of Neurobiology, Duke University Medical Center, Durham, North 
      Carolina 27710.
FAU - Cobb, John
AU  - Cobb J
AD  - Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 
      1N4, Canada jacobb@ucalgary.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxa11 protein, mouse)
RN  - 0 (Hoxd13 protein, mouse)
RN  - 0 (Hoxd9 protein, mouse)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Shox2 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - *Epistasis, Genetic
MH  - Extremities/*embryology
MH  - Gene Expression Regulation, Developmental
MH  - *Genes, Homeobox
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Humans
MH  - Mice
MH  - Mutation
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
PMC - PMC4224156
OTO - NOTNLM
OT  - SHOX
OT  - chondrogenesis
OT  - epistasis
OT  - fluorescence in situ hybridization
OT  - perichondrium
EDAT- 2014/09/14 06:00
MHDA- 2015/07/08 06:00
PMCR- 2015/11/01
CRDT- 2014/09/14 06:00
PHST- 2014/09/14 06:00 [entrez]
PHST- 2014/09/14 06:00 [pubmed]
PHST- 2015/07/08 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - genetics.114.167460 [pii]
AID - 167460 [pii]
AID - 10.1534/genetics.114.167460 [doi]
PST - ppublish
SO  - Genetics. 2014 Nov;198(3):1117-26. doi: 10.1534/genetics.114.167460. Epub 2014 
      Sep 11.