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Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion

Dudas, Marek; Kim, Jieun; Li, Wai-Yee; Nagy, Andre; Larsson, Jonas LU ; Karlsson, Stefan LU ; Chai, Yang and Kaartinen, Vesa (2006) In Developmental Biology 296(2). p.298-314
Abstract
Transforming growth factor beta (TGF-beta) proteins play important roles in morphogenesis of many cramofacial tissues; however, detailed biological mechanisms of TGF-beta action, particularly in vivo, are still poorly understood. Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the embryonic ectodermal and neural crest cell lineages. Failure in signaling via this receptor, either in the epithelium or in the mesenchyme, caused severe craniofacial defects including cleft palate. Moreover, the facial phenotypes of neural crest-specific Alk5 mutants included devastating facial cleft and appeared significantly more severe than the defects seen in corresponding mutants lacking the TGF-beta type II receptor (TGF beta II), a... (More)
Transforming growth factor beta (TGF-beta) proteins play important roles in morphogenesis of many cramofacial tissues; however, detailed biological mechanisms of TGF-beta action, particularly in vivo, are still poorly understood. Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the embryonic ectodermal and neural crest cell lineages. Failure in signaling via this receptor, either in the epithelium or in the mesenchyme, caused severe craniofacial defects including cleft palate. Moreover, the facial phenotypes of neural crest-specific Alk5 mutants included devastating facial cleft and appeared significantly more severe than the defects seen in corresponding mutants lacking the TGF-beta type II receptor (TGF beta II), a prototypical binding partner of ALK5. Our data indicate that ALK5 plays unique, non-redundant cell-autonomous roles during facial development. Remarkable divergence between Tgfbr2 and A1k5 phenotypes, together with our biochemical in vitro data, imply that (1) ALK5 mediates signaling of a diverse set of ligands not limited to the three isoforms of TGF-beta, and (2) ALK5 acts also in conjunction with type II receptors other than TGF beta RII. (c) 2006 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mandible, malformation, craniofacial, cranial neural crest, cleft palate, ALK5, cleft face, palatal fusion
in
Developmental Biology
volume
296
issue
2
pages
298 - 314
publisher
Elsevier
external identifiers
  • pmid:16806156
  • wos:000239980200002
  • scopus:33747078200
ISSN
1095-564X
DOI
10.1016/j.ydbio.2006.05.030
language
English
LU publication?
yes
id
3581fbbe-cd47-4ac5-a978-d197f4e7a08b (old id 395240)
date added to LUP
2007-10-02 13:46:03
date last changed
2019-10-16 01:40:42
@article{3581fbbe-cd47-4ac5-a978-d197f4e7a08b,
  abstract     = {Transforming growth factor beta (TGF-beta) proteins play important roles in morphogenesis of many cramofacial tissues; however, detailed biological mechanisms of TGF-beta action, particularly in vivo, are still poorly understood. Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the embryonic ectodermal and neural crest cell lineages. Failure in signaling via this receptor, either in the epithelium or in the mesenchyme, caused severe craniofacial defects including cleft palate. Moreover, the facial phenotypes of neural crest-specific Alk5 mutants included devastating facial cleft and appeared significantly more severe than the defects seen in corresponding mutants lacking the TGF-beta type II receptor (TGF beta II), a prototypical binding partner of ALK5. Our data indicate that ALK5 plays unique, non-redundant cell-autonomous roles during facial development. Remarkable divergence between Tgfbr2 and A1k5 phenotypes, together with our biochemical in vitro data, imply that (1) ALK5 mediates signaling of a diverse set of ligands not limited to the three isoforms of TGF-beta, and (2) ALK5 acts also in conjunction with type II receptors other than TGF beta RII. (c) 2006 Elsevier Inc. All rights reserved.},
  author       = {Dudas, Marek and Kim, Jieun and Li, Wai-Yee and Nagy, Andre and Larsson, Jonas and Karlsson, Stefan and Chai, Yang and Kaartinen, Vesa},
  issn         = {1095-564X},
  keyword      = {mandible,malformation,craniofacial,cranial neural crest,cleft palate,ALK5,cleft face,palatal fusion},
  language     = {eng},
  number       = {2},
  pages        = {298--314},
  publisher    = {Elsevier},
  series       = {Developmental Biology},
  title        = {Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion},
  url          = {http://dx.doi.org/10.1016/j.ydbio.2006.05.030},
  volume       = {296},
  year         = {2006},
}