PMID- 26079578
OWN - NLM
STAT- MEDLINE
DCOM- 20151029
LR  - 20231213
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 405
IP  - 1
DP  - 2015 Sep 1
TI  - Combining Foxc2 and Connexin37 deletions in mice leads to severe defects in 
      lymphatic vascular growth and remodeling.
PG  - 33-46
LID - S0012-1606(15)30010-5 [pii]
LID - 10.1016/j.ydbio.2015.06.004 [doi]
AB  - Connexins (Cxs), proteins that are vital for intercellular communication in 
      vertebrates, have recently been shown to play a critical role in lymphatic 
      development. However, our knowledge is currently limited regarding the functional 
      relationships of Cxs with other proteins and signaling pathways. Cell culture 
      studies have shown that Cx37 is necessary for coordinated activation of the 
      transcription factor NFATc1, which cooperates with Foxc2 (another transcription 
      factor) during lymphatic endothelial development. These data suggest that Cxs, 
      Foxc2, and NFATc1 are part of a common developmental pathway. Here, we present a 
      detailed characterization of Foxc2(+/-)Cx37(-/-) mice, demonstrating that 
      lymphatic network architecture and valve formation rely on the concurrent 
      embryonic expression and function of Foxc2 and Cx37. Foxc2(+/-)Cx37(-/-) mice 
      have lymphedema in utero, exhibit craniofacial abnormalities, show severe 
      dilation of intestinal lymphatics, display abnormal lacteal development, lack 
      lymphatic valves, and typically die perinatally (outcomes not seen in Foxc2(+/-) 
      or Cx37(-/-) mice separately). We provide a rigorous, quantitative documentation 
      of lymphatic vascular network changes that highlight the specific structural 
      alterations that occur in Foxc2(+/-)Cx37(-/-) mice. These data provide further 
      evidence suggesting that Foxc2 and Cx37 are elements in a common molecular 
      pathway directing lymphangiogenesis.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Kanady, John D
AU  - Kanady JD
AD  - Department of Physiology, University of Arizona, Tucson, AZ 85724, USA. 
      Electronic address: jkanady@email.arizona.edu.
FAU - Munger, Stephanie J
AU  - Munger SJ
AD  - Department of Physiology, University of Arizona, Tucson, AZ 85724, USA. 
      Electronic address: sjmunger@email.arizona.edu.
FAU - Witte, Marlys H
AU  - Witte MH
AD  - Department of Surgery, University of Arizona, Tucson, AZ 85724, USA. Electronic 
      address: lymph@email.arizona.edu.
FAU - Simon, Alexander M
AU  - Simon AM
AD  - Department of Physiology, University of Arizona, Tucson, AZ 85724, USA. 
      Electronic address: amsimon@email.arizona.edu.
LA  - eng
GR  - R01 HL064232/HL/NHLBI NIH HHS/United States
GR  - T32 HL007249/HL/NHLBI NIH HHS/United States
GR  - R01-HL64232/HL/NHLBI NIH HHS/United States
GR  - T32-HL007249/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150614
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Connexins)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (mesenchyme fork head 1 protein)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Body Patterning
MH  - Colon/pathology
MH  - Connexins/*deficiency/metabolism
MH  - Craniofacial Abnormalities/embryology/pathology
MH  - Edema/pathology
MH  - Embryo, Mammalian/abnormalities/pathology
MH  - Epithelial Cells/metabolism/pathology
MH  - Forkhead Transcription Factors/*deficiency/metabolism
MH  - *Gene Deletion
MH  - Intestine, Small/pathology
MH  - *Lymphangiogenesis
MH  - Lymphangioma/pathology
MH  - Lymphatic Vessels/*abnormalities/*embryology/pathology
MH  - Lymphography
MH  - Mesentery/pathology
MH  - Mice, Inbred C57BL
MH  - Mitosis
MH  - Skin/embryology/pathology
MH  - Gap Junction alpha-4 Protein
PMC - PMC4529811
MID - NIHMS705299
OTO - NOTNLM
OT  - Cx37
OT  - Foxc2
OT  - Lymphangiogenesis
OT  - Lymphatic valve
OT  - Lymphedema
OT  - Vascular development
EDAT- 2015/06/17 06:00
MHDA- 2015/10/30 06:00
PMCR- 2016/09/01
CRDT- 2015/06/17 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2015/06/03 00:00 [revised]
PHST- 2015/06/04 00:00 [accepted]
PHST- 2015/06/17 06:00 [entrez]
PHST- 2015/06/17 06:00 [pubmed]
PHST- 2015/10/30 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - S0012-1606(15)30010-5 [pii]
AID - 10.1016/j.ydbio.2015.06.004 [doi]
PST - ppublish
SO  - Dev Biol. 2015 Sep 1;405(1):33-46. doi: 10.1016/j.ydbio.2015.06.004. Epub 2015 
      Jun 14.