Retrograde BMP signaling regulates trigeminal sensory neuron identities and the formation of precise face maps.
Somatosensory information from the face is transmitted to the brain by trigeminal sensory neurons. It was previously unknown whether neurons innervating distinct areas of the face possess molecular differences. We have identified a set of genes differentially expressed along the dorsoventral axis of the embryonic mouse trigeminal ganglion and thus can be considered trigeminal positional identity markers. Interestingly, establishing some of the spatial patterns requires signals from the developing face. We identified bone morphogenetic protein 4 (BMP4) as one of these target-derived factors and showed that spatially defined retrograde BMP signaling controls the differential gene expressions in trigeminal neurons through both Smad4-independent and Smad4-dependent pathways. Mice lacking one of the BMP4-regulated transcription factors, Onecut2 (OC2), have defects in the trigeminal central projections representing the whiskers. Our results provide molecular evidence for both spatial patterning and retrograde regulation of gene expression in sensory neurons during the development of the somatosensory map.
Hodge
Liberty K
LK
Department of Cell Biology, Duke University Medical Center, Box 3709, Durham, NC 27710, USA.
Klassen
Matthew P
MP
Han
Bao-Xia
BX
Yiu
Glenn
G
Hurrell
Joanna
J
Howell
Audrey
A
Rousseau
Guy
G
Lemaigre
Frederic
F
Tessier-Lavigne
Marc
M
Wang
Fan
F
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001931:Brain Mapping; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005145:Face / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000196:embryology; D051155:Wnt1 Protein / Q000235:genetics
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C487964:ONECUT2 protein, mouse; D014157:Transcription Factors; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse