PMID- 10409510
OWN - NLM
STAT- MEDLINE
DCOM- 19991008
LR  - 20171116
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 126
IP  - 16
DP  - 1999 Aug
TI  - Ventral midline cells are required for the local control of commissural axon
      guidance in the mouse spinal cord.
PG  - 3649-59
AB  - Specialized cells at the midline of the central nervous system have been
      implicated in controlling axon projections in both invertebrates and vertebrates.
      To address the requirement for ventral midline cells in providing cues to
      commissural axons in mice, we have analyzed Gli2 mouse mutants, which lack
      specifically the floor plate and immediately adjacent interneurons. We show that 
      a Dbx1 enhancer drives tau-lacZ expression in a subpopulation of commissural
      axons and, using a reporter line generated from this construct, as well as DiI
      tracing, we find that commissural axons projected to the ventral midline in
      Gli2(-/-) embryos. Netrin1 mRNA expression was detected in Gli2(-/-) embryos and,
      although much weaker than in wild-type embryos, was found in a dorsally
      decreasing gradient. This result demonstrates that while the floor plate can
      serve as a source of long-range cues for C-axons in vitro, it is not required in 
      vivo for the guidance of commissural axons to the ventral midline in the mouse
      spinal cord. After reaching the ventral midline, most commissural axons remained 
      clustered in Gli2(-/-) embryos, although some were able to extend longitudinally.
      Interestingly, some of the longitudinally projecting axons in Gli2(-/-) embryos
      extended caudally and others rostrally at the ventral midline, in contrast to
      normal embryos in which virtually all commissural axons turn rostrally after
      crossing the midline. This finding indicates a critical role for ventral midline 
      cells in regulating the rostral polarity choice made by commissural axons after
      they cross the midline. In addition, we provide evidence that interactions
      between commissural axons and floor plate cells are required to modulate the
      localization of Nr-CAM and TAG-1 proteins on axons at the midline. Finally, we
      show that the floor plate is not required for the early trajectory of motoneurons
      or axons of the posterior commissure, whose projections are directed away from
      the ventral midline in both WT and Gli2(-/-) embryos, although they are less well
      organized in Gli2(-/-)mutants.
FAU - Matise, M P
AU  - Matise MP
AD  - Howard Hughes Medical Institute and Skirball Institute of Biomolecular Medicine, 
      Department of Cell Biology, New York University School of Medicine, New York, NY 
      10016, USA. matise@saturn.med.nyu.edu
FAU - Lustig, M
AU  - Lustig M
FAU - Sakurai, T
AU  - Sakurai T
FAU - Grumet, M
AU  - Grumet M
FAU - Joyner, A L
AU  - Joyner AL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Gli2 protein, mouse)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Zinc Finger Protein Gli2)
RN  - 158651-98-0 (Netrin-1)
SB  - IM
MH  - Animals
MH  - Axons/*physiology
MH  - Body Patterning
MH  - Gene Expression Regulation, Developmental
MH  - Interneurons/cytology/*physiology
MH  - Kruppel-Like Transcription Factors
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nerve Growth Factors/*genetics
MH  - Nerve Tissue Proteins/physiology
MH  - Netrin-1
MH  - RNA, Messenger/genetics
MH  - Spinal Cord/abnormalities/*embryology
MH  - Transcription Factors/deficiency/genetics/*physiology
MH  - Tumor Suppressor Proteins
MH  - Zinc Finger Protein Gli2
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
PST - ppublish
SO  - Development. 1999 Aug;126(16):3649-59.