Semaphorin signaling facilitates cleft formation in the developing salivary gland.
Semaphorin signaling plays integral roles in multiple developmental processes. Branching morphogenesis is one such role that has not been thoroughly explored. Here, we show in mice that functional blockage of neuropilin 1 (Npn1) inhibits cleft formation in the developing submandibular gland (SMG) cultured ex vivo. This Npn1-dependent morphogenesis is mediated by Sema3A and Sema3C in an additive manner, and can be abolished by decreasing the expression of plexin A2 or plexin D1. VEGF, another known Npn1 ligand, has no apparent effects on SMG development. FGF signaling, which also mediates SMG branching morphogenesis, acts in parallel with semaphorin signaling. Finally, in contrast to the effect of FGF signaling, we find that semaphorins do not stimulate the proliferation of SMG epithelial cells. Instead, the semaphorin signals act locally on the epithelial cells to facilitate SMG cleft formation.
Chung
Ling
L
Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yang
Tsung-Lin
TL
Huang
Hsiu-Ru
HR
Hsu
Su-Ming
SM
Cheng
Hwai-Jong
HJ
Huang
Pei-Hsin
PH
D000818:Animals; D002478:Cells, Cultured; D004628:Embryonic Structures / Q000254:growth & development*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D012469:Salivary Glands / Q000196:embryology*; D040121:Semaphorin-3A / Q000235:genetics / Q000502:physiology; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013363:Submandibular Gland / Q000196:embryology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492113:Plxna2 protein, mouse; C473552:Plxnd1 protein, mouse; D011956:Receptors, Cell Surface; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; D042461:Vascular Endothelial Growth Factor A; C510203:semaphorin 3C protein, mouse; C467480:vascular endothelial growth factor A, mouse; D039942:Neuropilin-1; D005346:Fibroblast Growth Factors