PMID- 23444360
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20220309
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 140
IP  - 6
DP  - 2013 Mar
TI  - Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development.
PG  - 1342-52
LID - 10.1242/dev.080630 [doi]
AB  - Wnt1-expressing progenitors generate midbrain dopamine (MbDA) and cerebellum (Cb) 
      neurons in distinct temporal windows and from spatially discrete progenitor 
      domains. It has been shown that Wnt1 and Lmx1a participate in a cross-regulatory 
      loop that is utilized during MbDA neuron development. However, Wnt1 expression 
      dynamically changes over time and precedes that of Lmx1a. The spatial and 
      temporal requirements of Wnt1 in development and specifically its requirement for 
      MbDA neurons remain to be determined. To address these issues, we generated a 
      conditional Wnt1 allele and temporally deleted Wnt1 coupled with genetic lineage 
      analysis. Using this approach, we show that patterning of the midbrain (Mb) and 
      Cb by Wnt1 occurs between the one-somite and the six- to eight-somite stages and 
      is solely dependent on Wnt1 function in the Mb, but not in the Cb. Interestingly, 
      an En1-derived domain persists after the early deletion of Wnt1 and mutant cells 
      express OTX2. However, the En1-derived Wnt1-mutant domain does not contain 
      LMX1a-expressing progenitors, and MbDA neurons are depleted. Thus, we demonstrate 
      an early requirement of Wnt1 for all MbDA neurons. Subsequently, we deleted Wnt1 
      in the ventral Mb and show a continued late requirement for Wnt1 in MbDA neuron 
      development, but not in LMX1a-expressing progenitors. Specifically, Wnt1 deletion 
      disrupts the birthdating of MbDA neurons and causes a depletion of MbDA neurons 
      positioned medially and a concomitant expansion of MbDA neurons positioned 
      laterally during embryogenesis. Collectively, our analyses resolve the spatial 
      and temporal function of Wnt1 in Mb and Cb patterning and in MbDA neuron 
      development in vivo.
FAU - Yang, Jasmine
AU  - Yang J
AD  - Department of Molecular Biology, Cell Biology and Biochemistry, Division of 
      Biology and Medicine, Brown University, 70 Ship Street, Providence, RI 02903, 
      USA.
FAU - Brown, Ashly
AU  - Brown A
FAU - Ellisor, Debra
AU  - Ellisor D
FAU - Paul, Erin
AU  - Paul E
FAU - Hagan, Nellwyn
AU  - Hagan N
FAU - Zervas, Mark
AU  - Zervas M
LA  - eng
GR  - P20 GM103468/GM/NIGMS NIH HHS/United States
GR  - T32 MH020068/MH/NIMH NIH HHS/United States
GR  - 8P20GM103468-04/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Wnt1 Protein)
SB  - IM
MH  - Animals
MH  - Body Patterning/genetics/physiology
MH  - Cell Differentiation/*genetics/physiology
MH  - Cerebellum/embryology/metabolism
MH  - Dopaminergic Neurons/metabolism/*physiology
MH  - Embryo, Mammalian
MH  - Female
MH  - Gene Expression Regulation, Developmental/physiology
MH  - Kinetics
MH  - Mesencephalon/cytology/*embryology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neural Stem Cells/metabolism/physiology
MH  - Organ Specificity/genetics
MH  - Pregnancy
MH  - Time Factors
MH  - Wnt1 Protein/genetics/metabolism/*physiology
PMC - PMC3585666
EDAT- 2013/02/28 06:00
MHDA- 2013/05/02 06:00
PMCR- 2014/03/15
CRDT- 2013/02/28 06:00
PHST- 2013/02/28 06:00 [entrez]
PHST- 2013/02/28 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
PHST- 2014/03/15 00:00 [pmc-release]
AID - 140/6/1342 [pii]
AID - 10.1242/dev.080630 [doi]
PST - ppublish
SO  - Development. 2013 Mar;140(6):1342-52. doi: 10.1242/dev.080630.