Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling.
Low-threshold mechanoreceptor neurons (LTMs) of the dorsal root ganglia (DRG) are essential for touch sensation. They form highly specialized terminations in the skin and display stereotyped projections in the spinal cord. Functionally defined LTMs depend on neurotrophin signaling for their postnatal survival and functioning, but how these neurons arise during development is unknown. Here, we show that specific types of LTMs can be identified shortly after DRG genesis by unique expression of the MafA transcription factor, the Ret receptor and coreceptor GFRalpha2, and find that their specification is Ngn2 dependent. In mice lacking Ret, these LTMs display early differentiation defects, as revealed by reduced MafA expression, and at later stages their central and peripheral projections are compromised. Moreover, in MafA mutants, a discrete subset of LTMs display altered expression of neurotrophic factor receptors. Our results provide evidence that genetic interactions involving Ret and MafA progressively promote the differentiation and diversification of LTMs.
Bourane
Steeve
S
INSERM U-583, F34091 Montpellier, France.
Garces
Alain
A
Venteo
Stephanie
S
Pattyn
Alexandre
A
Hubert
Thomas
T
Fichard
Agnes
A
Puech
Sylvie
S
Boukhaddaoui
Hassan
H
Baudet
Christel
C
Takahashi
Satoru
S
Valmier
Jean
J
Carroll
Patrick
P
D000344:Afferent Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism*; D012684:Sensory Thresholds / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014110:Touch / Q000502:physiology*
C494991:Gfra2 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D009414:Nerve Growth Factors; C491453:Nrg2 protein, mouse; D051096:Proto-Oncogene Proteins c-ret