Mechanisms of palatal epithelial seam disintegration by transforming growth factor (TGF) beta3.
TGFbeta3 signaling initiates and completes sequential phases of cellular differentiation that is required for complete disintegration of the palatal medial edge seam, that progresses between 14 and 17 embryonic days in the murine system, which is necessary in establishing confluence of the palatal stroma. Understanding the cellular mechanism of palatal MES disintegration in response to TGFbeta3 signaling will result in new approaches to defining the causes of cleft palate and other facial clefts that may result from failure of seam disintegration. We have isolated MES primary cells to study the details of MES disintegration mechanism by TGFbeta3 during palate development using several biochemical and genetic approaches. Our results demonstrate a novel mechanism of MES disintegration where MES, independently yet sequentially, undergoes cell cycle arrest, cell migration and apoptosis to generate immaculate palatal confluency during palatogenesis in response to robust TGFbeta3 signaling. The results contribute to a missing fundamental element to our base knowledge of the diverse roles of TGFbeta3 in functional and morphological changes that MES undergo during palatal seam disintegration. We believe that our findings will lead to more effective treatment of facial clefting.
Ahmed
Shaheen
S
Department of Oral Biology, College of Dentistry, The University of Nebraska Medical Center, 40th and Holdrege, Lincoln, NE 68583, USA.
Liu
Chang-Chih
CC
Nawshad
Ali
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D010159:Palate / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D053782:Transforming Growth Factor beta3 / Q000502:physiology*
D015820:Cadherins; D053782:Transforming Growth Factor beta3
Biochem Pharmacol. 2006 Nov 30;72(11):1396-404
16765323
Oncogene. 2006 Nov 23;25(55):7235-44
16799646
Curr Opin Cell Biol. 2001 Feb;13(1):76-84
11163137
J Histochem Cytochem. 2001 Mar;49(3):369-78
11181740
Cell. 1999 Jan 22;96(2):245-54
9988219
Dev Biol. 1999 Apr 15;208(2):530-45
10191064
Lab Anim Sci. 1999 Apr;49(2):137-43
10331542
Cell Motil Cytoskeleton. 1999;43(4):288-95
10423270
Development. 1999 Sep;126(17):3869-79
10433915
Biochem Biophys Res Commun. 2004 Dec 24;325(4):1136-44
15555546
Curr Top Dev Biol. 2005;66:65-133
15797452
J Cell Physiol. 2005 Jul;204(1):260-72
15690394
J Dent Res. 2005 Jun;84(6):526-31
15914589
Curr Opin Genet Dev. 2005 Jun;15(3):270-8
15917202
Cell. 2005 Jun 3;121(5):671-4
15935754
Arch Oral Biol. 2007 Jan;52(1):15-9
17055447
Acta Histochem. 2007;109(1):1-14
16962647
J Cell Sci. 2007 May 1;120(Pt 9):1646-53
17452626
Dev Biol. 2000 Feb 15;218(2):248-58
10656767
Dev Biol. 2000 Apr 15;220(2):343-57
10753521
Methods Mol Biol. 2000;135:357-63
10791331
Angle Orthod. 2000 Jun;70(3):181-2
10926427
Int J Dev Biol. 2000 Jun;44(4):397-402
10949049
Dev Biol. 2000 Dec 15;228(2):337-49
11112334
J Exp Med. 2000 Aug 21;192(4):571-80
10952727
Nature. 2001 Mar 29;410(6828):549-54
11279485
Am J Epidemiol. 2001 May 15;153(10):1007-15
11384957
Circulation. 2001 Jun 19;103(24):2879-81
11413073
J Mammary Gland Biol Neoplasia. 2001 Jan;6(1):67-82
11467453
Cell Tissue Res. 2002 Jan;307(1):1-14
11810309
J Biol Chem. 2002 Oct 11;277(41):38803-9
12151403
J Biol Chem. 2002 Nov 1;277(44):41686-92
12202478
J Cell Sci. 2002 Dec 15;115(Pt 24):4727-34
12432061
J Cell Biol. 2002 Dec 23;159(6):923-9
12486111
J Dent Res. 2003 Apr;82(4):289-92
12651933
Sci STKE. 2003 Jul 29;2003(193):PE31
12888619
Cancer Res. 2003 Nov 15;63(22):7791-8
14633705
Development. 2004 Jan;131(1):15-24
14645125
Chin Med J (Engl). 2003 Dec;116(12):1923-9
14687485
J Cell Biol. 2003 Dec 22;163(6):1291-301
14691138
Int J Dev Biol. 2004 Feb;48(1):39-46
15005573
Genes Dev. 2004 May 15;18(10):1131-43
15155580
Dev Dyn. 2004 Jul;230(3):529-34
15188437
J Clin Invest. 2004 Jun;113(12):1676-8
15199400
Int J Dev Biol. 2004 Jun;48(4):307-17
15300511
Development. 1988;103 Suppl:41-60
3074914
Development. 1990 Jul;109(3):585-95
2401212
Dev Biol. 1992 Dec;154(2):318-30
1385235
Nat Genet. 1995 Dec;11(4):409-14
7493021
Nat Genet. 1995 Dec;11(4):415-21
7493022
Arch Histol Cytol. 1995 Jun;58(2):191-203
7576871
Acta Anat (Basel). 1995;154(1):8-20
8714286
Dev Dyn. 1997 Jul;209(3):255-60
9215640
Cell. 1998 Sep 18;94(6):727-37
9753320
Int J Oncol. 1998 Dec;13(6):1247-52
9824639
J Dent Res. 2005 Aug;84(8):678-90
16040723
Dev Dyn. 2005 Sep;234(1):132-42
16010672
Dev Biol. 2005 Sep 15;285(2):490-5
16109396
Curr Opin Cell Biol. 2005 Dec;17(6):626-30
16219456
Oncogene. 2006 Mar 16;25(12):1763-74
16278674
Int J Dev Biol. 2006;50(5):491-7
16586350
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9918-23
16788063
J Biol Chem. 2006 Aug 11;281(32):22943-52
16754658
Dev Biol. 2006 Aug 15;296(2):298-314
16806156
Development. 2006 Sep;133(17):3341-7
16887819
Cancer Res. 2006 Sep 1;66(17):8617-24
16951175
Dev Biol. 2006 Sep 1;297(1):238-48
16780827
Cancer Res. 2006 Oct 1;66(19):9543-56
17018611