PMID- 21674568
OWN - NLM
STAT- MEDLINE
DCOM- 20111205
LR  - 20211203
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 89
IP  - 9
DP  - 2011 Sep
TI  - Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent 
      motor neuron production in mouse embryonic stem cell cultures.
PG  - 1363-74
LID - 10.1002/jnr.22675 [doi]
AB  - Pituitary adenylyl cyclase-activating peptide (PACAP; ADCYAP1) is a neuropeptide 
      that regulates a wide array of functions within the brain and periphery. We and 
      others have previously demonstrated that PACAP and its high-affinity receptor 
      PAC1 are expressed in the embryonic mouse neural tube, suggesting that PACAP 
      plays a role in early brain development. Moreover, we previously showed that 
      PACAP antagonizes the mitotic action of Sonic hedgehog (Shh) in postnatal 
      cerebellar granule precursors. In the present study, we demonstrate that PACAP 
      completely blocked Shh-dependent motor neuron generation from embryonic stem cell 
      cultures and reduced mRNA levels of the Shh target gene Gli-1 and several ventral 
      spinal cord patterning genes. In vivo examination of motor neuron and other 
      patterning markers in embryonic day 12.5 spinal cords of wild-type and 
      PACAP-deficient mice by immunofluorescence, on the other hand, revealed no 
      obvious alterations in expressions of Islet1/2, MNR2, Lim1/2, Nkx2.2, or Shh, 
      although the Pax6-positive area was slightly expanded in PACAP-deficient spinal 
      cord. Caspase-3 staining revealed low, and similar, numbers of cells undergoing 
      apoptosis in embryonic wild-type vs. PACAP-deficient spinal cords, whereas a 
      slight but significant increase in number of mitotic cells was observed in 
      PACAP-deficient mice. Thus, although PACAP has a strong capacity to counteract 
      Shh signaling and motor neuron production in vitro, corresponding patterning 
      defects associated with PACAP loss may be obscured by compensatory mechanisms.
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Hirose, Megumi
AU  - Hirose M
AD  - Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, 
      David Geffen School of Medicine, University of California, Los Angeles, CA 
      90095-7332, USA.
FAU - Niewiadomski, Pawel
AU  - Niewiadomski P
FAU - Tse, Gary
AU  - Tse G
FAU - Chi, Gloria C
AU  - Chi GC
FAU - Dong, Hongmei
AU  - Dong H
FAU - Lee, Alice
AU  - Lee A
FAU - Carpenter, Ellen M
AU  - Carpenter EM
FAU - Waschek, James A
AU  - Waschek JA
LA  - eng
GR  - R01 HD034475/HD/NICHD NIH HHS/United States
GR  - R01 CA110384/CA/NCI NIH HHS/United States
GR  - R01 CA110384-02/CA/NCI NIH HHS/United States
GR  - R01 CA110384-01A1/CA/NCI NIH HHS/United States
GR  - HD04612/HD/NICHD NIH HHS/United States
GR  - HD06576/HD/NICHD NIH HHS/United States
GR  - R01 CA110384-03/CA/NCI NIH HHS/United States
GR  - HD34475/HD/NICHD NIH HHS/United States
GR  - P30 HD004612/HD/NICHD NIH HHS/United States
GR  - R01 CA110384-04/CA/NCI NIH HHS/United States
GR  - P01 HD006576/HD/NICHD NIH HHS/United States
GR  - R01 CA110384-05/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110614
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Gli1 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Homeobox Protein Nkx-2.2)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (NKX2-2 protein, human)
RN  - 0 (Nkx2-2 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (Shh protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Embryonic Stem Cells/cytology/*metabolism
MH  - Hedgehog Proteins/*metabolism
MH  - Homeobox Protein Nkx-2.2
MH  - Homeodomain Proteins
MH  - Kruppel-Like Transcription Factors/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Motor Neurons/cytology/*metabolism
MH  - Nuclear Proteins
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/*physiology
MH  - Signal Transduction/physiology
MH  - Spinal Cord/cytology/embryology/metabolism
MH  - Transcription Factors
MH  - Zinc Finger Protein GLI1
PMC - PMC3131491
MID - NIHMS286427
EDAT- 2011/06/16 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/09/01
CRDT- 2011/06/16 06:00
PHST- 2011/03/21 00:00 [received]
PHST- 2011/03/31 00:00 [accepted]
PHST- 2011/06/16 06:00 [entrez]
PHST- 2011/06/16 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - 10.1002/jnr.22675 [doi]
PST - ppublish
SO  - J Neurosci Res. 2011 Sep;89(9):1363-74. doi: 10.1002/jnr.22675. Epub 2011 Jun 14.