The Journal of Neuroscience, September 15, 2001, 21(18):7079-7088
Transforming Growth Factor 
: A Promoter of Motoneuron Survival
of Potential Biological Relevance
Séverine
Boillée,
Josette
Cadusseau,
Muriel
Coulpier,
Gaël
Grannec, and
Marie-Pierre
Junier
Institut National de la Santé et de la Recherche
Médicale Unité 421, Faculté de Médecine, 94010 Créteil, France
Expression of transforming growth factor 
(TGF), a member of
the epidermal growth factor (EGF) family, is a general response of
adult murine motoneurons to genetic and experimental lesions, TGF
appearing as an inducer of astrogliosis in these situations. Here we
address the possibility that TGF expression is not specific to
pathological situations but may participate to the embryonic development of motoneurons. mRNA of TGF and its receptor, the EGF
receptor (EGFR), were detected by ribonuclease protection assay in the
ventral part of the cervical spinal cord from embryonic day 12 (E12)
until adult ages. Reverse transcription-PCR amplification of their
transcripts from immunopurified E15 motoneurons, associated with
in situ double-immunohistological assays, identified
embryonic motoneurons as cellular sources of the TGF-EGFR couple.
In vitro, TGF promoted the survival of immunopurified
E15 motoneurons in a dose-dependent manner, with a magnitude similar to
BDNF neuroprotective effects at equivalent concentrations. In a
transgenic mouse expressing a human TGF transgene under the control
of the metallothionein 1 promoter, axotomy of the facial nerve provoked
significantly less degeneration in the relevant motor pool of
1-week-old mice than in wild-type animals. No protection was
observed in neonates, when the transgene exhibits only weak expression
levels in the brainstem. In conclusion, our results point to TGF as
a physiologically relevant candidate for a neurotrophic role on
developing motoneurons. Its expression by the embryonic motoneurons,
which also synthesize its receptor, suggests that this chemokine is
endowed with the capability to promote motoneuron survival in an
autocrine-paracrine manner.
Key words:
EGF; EGFR; erbB1; development; facial nucleus; spinal
cord
Copyright © 2001 Society for Neuroscience 0270-6474/01/21187079-10$05.00/0
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