PMID- 10430909
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 16
DP  - 1999 Aug 3
TI  - A vital role for glycosphingolipid synthesis during development and
      differentiation.
PG  - 9142-7
AB  - Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many
      cell membrane events, including cellular interactions, signaling, and
      trafficking. We have investigated their roles in development and differentiation 
      by eliminating the major synthesis pathway of GSLs through targeted disruption of
      the Ugcg gene encoding glucosylceramide synthase. In the absence of GSL
      synthesis, embryogenesis proceeded well into gastrulation with differentiation
      into primitive germ layers and patterning of the embryo but was abruptly halted
      by a major apoptotic process. In vivo, embryonic stem cells deficient in GSL
      synthesis were again able to differentiate into endodermal, mesodermal, and
      ectodermal derivatives but were strikingly deficient in their ability to form
      well differentiated tissues. In vitro, however, hematopoietic and neuronal
      differentiation could be induced. The results demonstrate that the synthesis of
      GSL structures is essential for embryonic development and for the differentiation
      of some tissues and support the concept that GSLs are involved in crucial cell
      interactions mediating these processes.
FAU - Yamashita, T
AU  - Yamashita T
AD  - Genetics of Development and Disease Branch, National Institute of Diabetes and
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892,
      USA.
FAU - Wada, R
AU  - Wada R
FAU - Sasaki, T
AU  - Sasaki T
FAU - Deng, C
AU  - Deng C
FAU - Bierfreund, U
AU  - Bierfreund U
FAU - Sandhoff, K
AU  - Sandhoff K
FAU - Proia, R L
AU  - Proia RL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Glycosphingolipids)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 2.4.1.80 (ceramide glucosyltransferase)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Differentiation/genetics
MH  - Embryo, Mammalian/pathology/physiology
MH  - Embryonic and Fetal Development/genetics/*physiology
MH  - Gastrula/cytology/*physiology
MH  - Genomic Library
MH  - Genotype
MH  - Glucosyltransferases/deficiency/genetics/*metabolism
MH  - Glycosphingolipids/*biosynthesis/physiology
MH  - In Situ Hybridization
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Knockout
MH  - Polymerase Chain Reaction
MH  - Stem Cells/pathology
MH  - Teratoma/genetics/pathology
PMC - PMC17746
EDAT- 1999/08/04 00:00
MHDA- 1999/08/04 00:01
CRDT- 1999/08/04 00:00
PHST- 1999/08/04 00:00 [pubmed]
PHST- 1999/08/04 00:01 [medline]
PHST- 1999/08/04 00:00 [entrez]
AID - 10.1073/pnas.96.16.9142 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9142-7. doi: 10.1073/pnas.96.16.9142.