title: Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling.
abstract: 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.
authors.affiliation: INSERM U-583, F34091 Montpellier, France.
authors.forename: Steeve
authors.initials: S
authors.lastname: Bourane
authors.forename: Alain
authors.initials: A
authors.lastname: Garces
authors.forename: Stephanie
authors.initials: S
authors.lastname: Venteo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Thomas
authors.initials: T
authors.lastname: Hubert
authors.forename: Agnes
authors.initials: A
authors.lastname: Fichard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Puech
authors.forename: Hassan
authors.initials: H
authors.lastname: Boukhaddaoui
authors.forename: Christel
authors.initials: C
authors.lastname: Baudet
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Jean
authors.initials: J
authors.lastname: Valmier
authors.forename: Patrick
authors.initials: P
authors.lastname: Carroll
mesh_terms: 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*
chemical_list: 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