PMID- 10479450
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20091119
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 213
IP  - 2
DP  - 1999 Sep 15
TI  - Multiple roles for activin-like kinase-2 signaling during mouse embryogenesis.
PG  - 314-26
AB  - The members of the transforming growth factor-beta (TGF-beta) superfamily are
      secreted proteins that interact with cell-surface receptors to elicit signals
      that regulate a variety of biological processes during vertebrate embryogenesis. 
      Alk2, also known as ActRIA, Tsk7L, and SKR1, encodes a type I TGF-beta family
      receptor for activins and BMP-7. Initially, Alk2 transcripts are detected in the 
      visceral endoderm of gastrula stage mouse embryos, suggesting a signaling role in
      extraembryonic tissues during development. To study the role of Alk2 during
      mammalian development, Alk2 mutant mice were generated. After embryonic day 9.5
      (E9.5), no homozygous mutants were recovered from heterozygote matings.
      Homozygous mutants with morphological defects were first detected at E7.0 and
      were smaller than controls. Morphological and molecular examination demonstrated 
      that Alk2 mutant embryos formed a primitive streak, although abnormally
      thickened, and were arrested in their development around the late streak stage.
      These gastrulation defects were rescued in chimeric embryos generated by
      injection of Alk2 mutant embryonic stem (ES) cells into wild-type blastocysts.
      This rescue of gastrulation defects was also observed in chimeric embryos
      generated by aggregation of Alk2 homozygous mutant ES cells with tetraploid
      wild-type embryos. However, at E9.5, these embryos that were completely
      ES-derived also had defects. In contrast, chimeric embryos generated by injection
      of wild-type ES cells into Alk2 mutant blastocysts did not show rescue of the
      gastrulation defects. These results suggest that signaling through this type I
      receptor is essential in extraembryonic tissues at the time of gastrulation for
      normal mesoderm formation and also suggest that subsequent Alk2 signaling is
      essential for normal development after gastrulation.
CI  - Copyright 1999 Academic Press.
FAU - Mishina, Y
AU  - Mishina Y
AD  - Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer
      Center, Houston, Texas, 77030, USA.
FAU - Crombie, R
AU  - Crombie R
FAU - Bradley, A
AU  - Bradley A
FAU - Behringer, R R
AU  - Behringer RR
LA  - eng
GR  - HD30284/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.30 (Activin Receptors, Type I)
SB  - IM
MH  - Activin Receptors, Type I
MH  - Animals
MH  - *Embryonic and Fetal Development
MH  - Gastrula/physiology
MH  - Mice
MH  - Mutation
MH  - Receptors, Growth Factor/*physiology
MH  - Signal Transduction/*physiology
MH  - Transforming Growth Factor beta/*physiology
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1006/dbio.1999.9378 [doi]
AID - S0012-1606(99)99378-8 [pii]
PST - ppublish
SO  - Dev Biol. 1999 Sep 15;213(2):314-26. doi: 10.1006/dbio.1999.9378.