PMID- 18256198
OWN - NLM
STAT- MEDLINE
DCOM- 20080529
LR  - 20220321
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 135
IP  - 6
DP  - 2008 Mar
TI  - R-spondin 2 is required for normal laryngeal-tracheal, lung and limb 
      morphogenesis.
PG  - 1049-58
LID - 10.1242/dev.013359 [doi]
AB  - Herein, we demonstrate that Lrp6-mediated R-spondin 2 signaling through the 
      canonical Wnt pathway is required for normal morphogenesis of the respiratory 
      tract and limbs. We show that the footless insertional mutation creates a severe 
      hypomorphic R-spondin 2 allele (Rspo2(Tg)). The predicted protein encoded by 
      Rspo2(Tg) neither bound the cell surface nor activated the canonical Wnt 
      signaling reporter TOPFLASH. Rspo2 activation of TOPFLASH was dependent upon the 
      second EGF-like repeat of Lrp6. Rspo2(Tg/Tg) mice had severe malformations of 
      laryngeal-tracheal cartilages, limbs and palate, and lung hypoplasia consistent 
      with sites of Rspo2 expression. Rspo2(Tg/Tg) lung defects were associated with 
      reduced branching, a reduction in TOPGAL reporter activity, and reduced 
      expression of the downstream Wnt target Irx3. Interbreeding the Rspo2(Tg) and 
      Lrp6(-) alleles resulted in more severe defects consisting of marked lung 
      hypoplasia and absence of tracheal-bronchial rings, laryngeal structures and all 
      limb skeletal elements.
FAU - Bell, Sheila M
AU  - Bell SM
AD  - Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's 
      Hospital Medical Center and The University of Cincinnati College of Medicine, 
      Cincinnati, OH 45229, USA.
FAU - Schreiner, Claire M
AU  - Schreiner CM
FAU - Wert, Susan E
AU  - Wert SE
FAU - Mucenski, Michael L
AU  - Mucenski ML
FAU - Scott, William J
AU  - Scott WJ
FAU - Whitsett, Jeffrey A
AU  - Whitsett JA
LA  - eng
GR  - HD-24517/HD/NICHD NIH HHS/United States
GR  - HL-75770/HL/NHLBI NIH HHS/United States
GR  - HL090156/HL/NHLBI NIH HHS/United States
GR  - HL61646/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080206
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-6)
RN  - 0 (Lrp6 protein, mouse)
RN  - 0 (RSPO2 protein, mouse)
RN  - 0 (Sp8 protein, mouse)
RN  - 0 (Thrombospondins)
RN  - 0 (Transcription Factors)
RN  - 0 (Wnt Proteins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA, Complementary/genetics
MH  - DNA-Binding Proteins/deficiency/genetics
MH  - Extremities/*embryology
MH  - Female
MH  - LDL-Receptor Related Proteins/deficiency/genetics/physiology
MH  - Larynx/abnormalities/*embryology
MH  - Limb Deformities, Congenital/etiology/genetics
MH  - Low Density Lipoprotein Receptor-Related Protein-6
MH  - Lung/abnormalities/*embryology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Morphogenesis
MH  - Mutagenesis, Insertional
MH  - Pregnancy
MH  - Signal Transduction
MH  - Thrombospondins/deficiency/genetics/*physiology
MH  - Trachea/abnormalities/*embryology
MH  - Transcription Factors/deficiency/genetics
MH  - Wnt Proteins/physiology
EDAT- 2008/02/08 09:00
MHDA- 2008/05/30 09:00
CRDT- 2008/02/08 09:00
PHST- 2008/02/08 09:00 [pubmed]
PHST- 2008/05/30 09:00 [medline]
PHST- 2008/02/08 09:00 [entrez]
AID - dev.013359 [pii]
AID - 10.1242/dev.013359 [doi]
PST - ppublish
SO  - Development. 2008 Mar;135(6):1049-58. doi: 10.1242/dev.013359. Epub 2008 Feb 6.