PMID- 10903171
OWN - NLM
STAT- MEDLINE
DCOM- 20000919
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 127
IP  - 16
DP  - 2000 Aug
TI  - Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice 
      implicates a novel mesenchymal structure with putative instructive properties in 
      villus morphogenesis.
PG  - 3457-66
AB  - Development of the gastrointestinal (GI) tract depends on reciprocal 
      epithelial-mesenchymal cell signaling. Here, we demonstrate a role for 
      platelet-derived growth factor-A (PDGF-A) and its receptor, PDGFR-(alpha), in 
      this process. Mice lacking PDGF-A or PDGFR-(alpha) were found to develop an 
      abnormal GI mucosal lining, including fewer and misshapen villi and loss of 
      pericryptal mesenchyme. Onset of villus morphogenesis correlated with the 
      formation of clusters of PDGFR-(alpha) positive cells, 'villus clusters', which 
      remained located at the tip of the mesenchymal core of the growing villus. Lack 
      of PDGF-A or PDGFR-(alpha) resulted in progressive depletion of PDGFR-(alpha) 
      positive mesenchymal cells, the formation of fewer villus clusters, and premature 
      expression of smooth muscle actin (SMA) in the villus mesenchyme. We found that 
      the villus clusters were postmitotic, expressed BMP-2 and BMP-4, and that their 
      formation correlated with downregulated DNA synthesis in adjacent intestinal 
      epithelium. We propose a model in which villus morphogenesis is initiated as a 
      result of aggregation of PDGFR-(&agr;) positive cells into cell clusters that 
      subsequently function as mesenchymal centers of signaling to the epithelium. The 
      role of PDGF-A seems to be to secure renewal of PDGFR-(alpha) positive cells when 
      they are consumed in the initial rounds of cluster formation.
FAU - Karlsson, L
AU  - Karlsson L
AD  - Department of Medical Biochemistry, Goteborg University, Medicinaregatan 9A, Box 
      440, SE 405 30 Goteborg, Sweden. Linda. Karlsson@medkem.gu.se
FAU - Lindahl, P
AU  - Lindahl P
FAU - Heath, J K
AU  - Heath JK
FAU - Betsholtz, C
AU  - Betsholtz C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Bmp2 protein, mouse)
RN  - 0 (Bmp4 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (platelet-derived growth factor A)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Protein 4
MH  - Bone Morphogenetic Proteins/genetics
MH  - Cell Differentiation
MH  - Cell Division
MH  - Digestive System/embryology
MH  - Gene Expression Profiling
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/*embryology
MH  - Mesoderm
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microvilli
MH  - Morphogenesis
MH  - Muscle, Smooth/cytology
MH  - Platelet-Derived Growth Factor/genetics/*physiology
MH  - Receptor, Platelet-Derived Growth Factor alpha/*physiology
MH  - *Transforming Growth Factor beta
EDAT- 2000/07/21 11:00
MHDA- 2000/09/23 11:01
CRDT- 2000/07/21 11:00
PHST- 2000/07/21 11:00 [pubmed]
PHST- 2000/09/23 11:01 [medline]
PHST- 2000/07/21 11:00 [entrez]
AID - 10.1242/dev.127.16.3457 [doi]
PST - ppublish
SO  - Development. 2000 Aug;127(16):3457-66. doi: 10.1242/dev.127.16.3457.