title: Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.
abstract: The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.
authors: Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL 32610, USA.
authors: Kyung-Suk
authors: KS
authors: Choi
authors: Brian D
authors: BD
authors: Harfe
references: J Anat. 1995 Feb;186 ( Pt 1):111-21
references: 7649807
references: Development. 2002 Jul;129(13):3137-46
references: 12070089
references: Development. 2000 Nov;127(22):4775-85
references: 11044393
references: Acta Anat (Basel). 1990;137(2):114-23
references: 2316326
references: Spine (Phila Pa 1976). 2006 Aug 15;31(18):2151-61
references: 16915105
references: J Orthop Res. 2005 Sep;23(5):1112-9
references: 15936916
references: Dev Cell. 2008 Apr;14(4):624-32
references: 18410737
references: Adv Anat Embryol Cell Biol. 1988;112:1-99
references: 3055848
references: Anat Embryol (Berl). 1995 Jul;192(1):53-62
references: 7486001
references: Cell. 2001 Jul 27;106(2):781-92
references: 11517919
references: Methods Enzymol. 1993;225:361-73
references: 8231863
references: J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:21-4
references: 16595438
references: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6382-7
references: 17409191
references: Dev Dyn. 1995 Jul;203(3):253-310
references: 8589427
references: Tissue Eng. 2003 Aug;9(4):667-77
references: 13678445
references: Nat Neurosci. 2002 Feb;5(2):103-10
references: 11788837
references: Development. 1997 Jan;124(2):363-71
references: 9053312
references: J Cell Biol. 1998 Nov 30;143(5):1399-412
references: 9832566
references: J Embryol Exp Morphol. 1980 Feb;55:227-45
references: 7373196
references: Development. 2000 Feb;127(3):543-8
references: 10631175
references: Development. 2001 Dec;128(24):5099-108
references: 11748145
references: Cell. 2004 Aug 20;118(4):517-28
references: 15315763
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: Development. 2003 Mar;130(6):1135-48
references: 12571105
references: Genes Dev. 1999 Jan 15;13(2):225-37
references: 9925646
references: Development. 1998 Feb;125(3):495-505
references: 9425144
references: Spine (Phila Pa 1976). 2009 Mar 1;34(5):456-62
references: 19212276
references: Development. 1999 Dec;126(23):5399-408
references: 10556064
references: Dev Dyn. 2008 Dec;237(12):3953-8
references: 19035356
references: Genes Dev. 2001 Dec 1;15(23):3059-87
references: 11731473
references: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9695-700
references: 10449756
references: Nature. 1996 Oct 3;383(6599):407-13
references: 8837770
references: Development. 1994 May;120(5):1109-21
references: 8026324
references: Edinb Med J. 1953 Aug;60(8):341-64
references: 13083579