Zeb family members and boundary cap cells underlie developmental plasticity of sensory nociceptive neurons.
Dorsal root ganglia (DRG) sensory neurons arise from heterogeneous precursors that differentiate in two neurogenic waves, respectively controlled by Neurog2 and Neurog1. We show here that transgenic mice expressing a Zeb1/2 dominant-negative form (DBZEB) exhibit reduced numbers of nociceptors and altered pain sensitivity. This reflects an early impairment of Neurog1-dependent neurogenesis due to the depletion of specific sensory precursor pools, which is slightly later partially compensated by the contribution of boundary cap cells (BCCs). Indeed, combined DBZEB expression and genetic BCCs ablation entirely deplete second wave precursors and, in turn, nociceptors, thus recapitulating the Neurog1(-/-) neuronal phenotype. Altogether, our results uncover roles for Zeb family members in the developing DRGs; they show that the Neurog1-dependent sensory neurogenesis can be functionally partitioned in two successive phases; and finally, they illustrate plasticity in the developing peripheral somatosensory system supported by the BCCs, thereby providing a rationale for sensory precursor diversity.
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France; Université de Toulouse, Centre de Biologie du Développement, UMR5547 CNRS, 31062 Toulouse, France.
David
D
Ohayon
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France.
Stéphanie
S
Ventéo
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France.
Corinne
C
Sonrier
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France.
Pierre-André
PA
Lafon
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France.
Alain
A
Garcès
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France; Université Montpellier 2, 34091 Montpellier, France.
Jean
J
Valmier
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France; Université Montpellier 2, 34091 Montpellier, France.
Cyril
C
Rivat
INSERM U1024, Ecole Normale Supérieure, 75230 Paris, France.
Piotr
P
Topilko
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France.
Patrick
P
Carroll
INSERM U1051, Institut des Neurosciences de Montpellier, 34091 Montpellier, France. Electronic address: alexandre.pattyn@inserm.fr.
Alexandre
A
Pattyn
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; C519422:ZEB1 protein, mouse; C120602:ZEB2 protein, mouse; C486336:Neurog1 protein, mouse