PMID- 10654602
OWN - NLM
STAT- MEDLINE
DCOM- 20000303
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 127
IP  - 1
DP  - 2000 Jan
TI  - Retinoic acid synthesis and hindbrain patterning in the mouse embryo.
PG  - 75-85
AB  - Targeted disruption of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene
      precludes embryonic retinoic acid (RA) synthesis, leading to midgestational
      lethality (Niederreither, K., Subbarayan, V., Dolle, P. and Chambon, P. (1999).
      Nature Genet. 21, 444-448). We describe here the effects of this RA deficiency on
      the development of the hindbrain and associated neural crest. Morphological
      segmentation is impaired throughout the hindbrain of Raldh2-/- embryos, but its
      caudal portion becomes preferentially reduced in size during development.
      Specification of the midbrain region and of the rostralmost rhombomeres is
      apparently normal in the absence of RA synthesis. In contrast, marked alterations
      are seen throughout the caudal hindbrain of mutant embryos. Instead of being
      expressed in two alternate rhombomeres (r3 and r5), Krox20 is expressed in a
      single broad domain, correlating with an abnormal expansion of the r2-r3 marker
      Meis2. Instead of forming a defined r4, Hoxb1- and Wnt8A-expressing cells are
      scattered throughout the caudal hindbrain, whereas r5/r8 markers such as kreisler
      or group 3/4 Hox genes are undetectable or markedly downregulated. Lack of
      alternate Eph receptor gene expression could explain the failure to establish
      rhombomere boundaries. Increased apoptosis and altered migratory pathways of the 
      posterior rhombencephalic neural crest cells are associated with impaired
      branchial arch morphogenesis in mutant embryos. We conclude that RA produced by
      the embryo is required to generate posterior cell fates in the developing mouse
      hindbrain, its absence leading to an abnormal r3 (and, to a lesser extent, r4)
      identity of the caudal hindbrain cells.
FAU - Niederreither, K
AU  - Niederreither K
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire,
      CNRS/INSERM/ULP/College de France, CU de Strasbourg.
FAU - Vermot, J
AU  - Vermot J
FAU - Schuhbaur, B
AU  - Schuhbaur B
FAU - Chambon, P
AU  - Chambon P
FAU - Dolle, P
AU  - Dolle P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Avian Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (Ephrin-A2)
RN  - 0 (Ephrin-A4)
RN  - 0 (HOXB1 homeodomain protein)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hox3 protein, Ciona intestinalis)
RN  - 0 (MafB Transcription Factor)
RN  - 0 (Mafb protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.2.- (Aldehyde Oxidoreductases)
RN  - EC 1.2.1.36 (Retinal Dehydrogenase)
SB  - IM
MH  - Aldehyde Oxidoreductases/genetics
MH  - Animals
MH  - *Avian Proteins
MH  - Body Patterning/*physiology
MH  - Cell Death
MH  - Cell Differentiation
MH  - DNA-Binding Proteins/genetics
MH  - Early Growth Response Protein 2
MH  - Ephrin-A2
MH  - Ephrin-A4
MH  - Gene Expression Regulation, Developmental
MH  - Homeodomain Proteins/genetics
MH  - MafB Transcription Factor
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neural Crest
MH  - Neurons/cytology
MH  - *Oncogene Proteins
MH  - Phenotype
MH  - Retinal Dehydrogenase
MH  - Rhombencephalon/*embryology
MH  - Transcription Factors/genetics
MH  - *Tretinoin
EDAT- 2000/02/02 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
AID - 10.1242/dev.127.1.75 [doi]
PST - ppublish
SO  - Development. 2000 Jan;127(1):75-85. doi: 10.1242/dev.127.1.75.