PMID- 23019366
OWN - NLM
STAT- MEDLINE
DCOM- 20121205
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 39
DP  - 2012 Sep 25
TI  - Hedgehog-responsive mesenchymal clusters direct patterning and emergence of 
      intestinal villi.
PG  - 15817-22
AB  - In the adult intestine, an organized array of finger-like projections, called 
      villi, provide an enormous epithelial surface area for absorptive function. Villi 
      first emerge at embryonic day (E) 14.5 from a previously flat luminal surface. 
      Here, we analyze the cell biology of villus formation and examine the role of 
      paracrine epithelial Hedgehog (Hh) signals in this process. We find that, before 
      villus emergence, tight clusters of Hh-responsive mesenchymal cells form just 
      beneath the epithelium. Cluster formation is dynamic; clusters first form 
      dorsally and anteriorly and spread circumferentially and posteriorly. Statistical 
      analysis of cluster distribution reveals a patterned array; with time, new 
      clusters form in spaces between existing clusters, promoting approximately four 
      rounds of villus emergence by E18.5. Cells within mesenchymal clusters express 
      Patched1 and Gli1, as well as Pdgfralpha, a receptor previously shown to participate 
      in villus development. BrdU-labeling experiments show that clusters form by 
      migration and aggregation of Hh-responsive cells. Inhibition of Hh signaling 
      prevents cluster formation and villus development, but does not prevent emergence 
      of villi in areas where clusters have already formed. Conversely, increasing Hh 
      signaling increases the size of villus clusters and results in exceptionally wide 
      villi. We conclude that Hh signals dictate the initial aspects of the formation 
      of each villus by controlling mesenchymal cluster aggregation and regulating 
      cluster size.
FAU - Walton, Katherine D
AU  - Walton KD
AD  - Department of Cell and Developmental Biology, University of Michigan Medical 
      School, Ann Arbor, MI 48109, USA.
FAU - Kolterud, Asa
AU  - Kolterud A
FAU - Czerwinski, Michael J
AU  - Czerwinski MJ
FAU - Bell, Michael J
AU  - Bell MJ
FAU - Prakash, Ajay
AU  - Prakash A
FAU - Kushwaha, Juhi
AU  - Kushwaha J
FAU - Grosse, Ann S
AU  - Grosse AS
FAU - Schnell, Santiago
AU  - Schnell S
FAU - Gumucio, Deborah L
AU  - Gumucio DL
LA  - eng
GR  - T32-HL07622/HL/NHLBI NIH HHS/United States
GR  - P60 DK-20572/DK/NIDDK NIH HHS/United States
GR  - P60 DK020572/DK/NIDDK NIH HHS/United States
GR  - R01 DK065850/DK/NIDDK NIH HHS/United States
GR  - T32-HL07505/HL/NHLBI NIH HHS/United States
GR  - T32 GM007315/GM/NIGMS NIH HHS/United States
GR  - T32 HL007622/HL/NHLBI NIH HHS/United States
GR  - P01 DK062041/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120910
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Gli1 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Animals
MH  - Hedgehog Proteins/genetics/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/cytology/*metabolism
MH  - Kruppel-Like Transcription Factors/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics/metabolism
MH  - Receptors, Cell Surface/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - Zinc Finger Protein GLI1
PMC - PMC3465418
COIS- The authors declare no conflict of interest.
EDAT- 2012/09/29 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/03/25
CRDT- 2012/09/29 06:00
PHST- 2012/09/29 06:00 [entrez]
PHST- 2012/09/29 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/03/25 00:00 [pmc-release]
AID - 1205669109 [pii]
AID - 201205669 [pii]
AID - 10.1073/pnas.1205669109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15817-22. doi: 
      10.1073/pnas.1205669109. Epub 2012 Sep 10.