Embryonic mouse blood flow and oxygen correlate with early pancreatic differentiation.
The mammalian embryo represents a fundamental paradox in biology. Its location within the uterus, especially early during development when embryonic cardiovascular development and placental blood flow are not well-established, leads to an obligate hypoxic environment. Despite this hypoxia, the embryonic cells are able to undergo remarkable growth, morphogenesis, and differentiation. Recent evidence suggests that embryonic organ differentiation, including pancreatic β-cells, is tightly regulated by oxygen levels. Since a major determinant of oxygen tension in mammalian embryos after implantation is embryonic blood flow, here we used a novel survivable in utero intracardiac injection technique to deliver a vascular tracer to living mouse embryos. Once injected, the embryonic heart could be visualized to continue contracting normally, thereby distributing the tracer specifically only to those regions where embryonic blood was flowing. We found that the embryonic pancreas early in development shows a remarkable paucity of blood flow and that the presence of blood flow correlates with the differentiation state of the developing pancreatic epithelial cells in the region of the blood flow.
Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, 45th Street and Penn Avenue, Pittsburgh, PA 15201, USA.
Sohail R
SR
Shah
Farzad
F
Esni
Adam
A
Jakub
Jose
J
Paredes
Nikesh
N
Lath
Marcus
M
Malek
Douglas A
DA
Potoka
Krishna
K
Prasadan
Pier G
PG
Mastroberardino
Chiyo
C
Shiota
Ping
P
Guo
Kelly A
KA
Miller
David J
DJ
Hackam
R Cartland
RC
Burns
Sidhartha S
SS
Tulachan
George K
GK
Gittes
D000818:Animals; D057791:Cardiac Imaging Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000098:blood supply*; D005452:Fluoresceins / Q000008:administration & dosage; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism*; D010179:Pancreas / Q000098:blood supply / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D037121:Plant Lectins / Q000008:administration & dosage; D018084:Ultrasonography, Interventional / Q000379:methods*
D005452:Fluoresceins; D037121:Plant Lectins; C034981:tomato lectin; D010100:Oxygen