Abstract

Neural crest cells (NCCs) are ectodermally derived stem cells that differentiate into a wealth ofderivatives. NCCs from the cranial region of higher vertebrates generate cartilage and bone.Trunk NCCs don't generate bone or cartilage under normal development, but they can beinduced to do so in vitro, or when experimentally grafted in specific bone forming territories ofthe cranium. We have recently shown that the induction of cranial NCCs occurs duringgastrulation, much earlier than previously thought (Basch et al. 2006). Additionally we uncover aneural crest induction mechanism independent of mesodermal and neural tissues. These resultsdepart from current dogmas of neural crest induction and provide a new timeframe for NCCsdevelopment.
The aim of this proposal is to identify the molecular principles governing the chondrogenicdifferentiation potential of. this critical stem cell for vertebrate development. We propose tochallenge the bone and cartilage potential of trunk NCCs through grafting strategies to prove therole of early signals of induction. Then we will test the effects of caudalizing signals (FGF andWnt) in the chondrogenic differentiation potential of both trunk and cranial NCC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR046032-10
Application #
7609122
Study Section
Special Emphasis Panel (ZAR1)
Project Start
2008-04-01
Project End
2009-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
10
Fiscal Year
2008
Total Cost
$48,619
Indirect Cost

  Institution

Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Zhu, Meiling; Sun, Ben-Hua; Saar, Katarzyna et al. (2016) Deletion of Rac in Mature Osteoclasts Causes Osteopetrosis, an Age-Dependent Change in Osteoclast Number, and a Reduced Number of Osteoblasts In Vivo. J Bone Miner Res 31:864-73
Belinsky, Glenn S; Sreekumar, Bharath; Andrejecsk, Jillian W et al. (2016) Pigment epithelium-derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. FASEB J 30:2837-48
Kim, Jae Geun; Sun, Ben-Hua; Dietrich, Marcelo O et al. (2015) AgRP Neurons Regulate Bone Mass. Cell Rep 13:8-14
Protiva, Petr; Gong, Jingjing; Sreekumar, Bharath et al. (2015) Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/?-catenin Signaling in the Liver. Cell Mol Gastroenterol Hepatol 1:535-549.e14
Ardeshirpour, Laleh; Dumitru, Cristina; Dann, Pamela et al. (2015) OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk Production or Maternal Calcium Metabolism. Endocrinology 156:2762-73
Meijome, Tomas E; Hooker, R Adam; Cheng, Ying-Hua et al. (2015) GATA-1 deficiency rescues trabecular but not cortical bone in OPG deficient mice. J Cell Physiol 230:783-90
Wang, Meina; Nasiri, Ali R; Broadus, Arthur E et al. (2015) Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing. Bone 81:104-111
Yao, Chen; Yao, Gang-Qing; Sun, Ben-Hua et al. (2014) The transcription factor T-box 3 regulates colony-stimulating factor 1-dependent Jun dimerization protein 2 expression and plays an important role in osteoclastogenesis. J Biol Chem 289:6775-90
McCarthy, Thomas L; Yun, Zhong; Madri, Joseph A et al. (2014) Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts. Gene 539:141-51
Wang, Meina; Nasiri, Ali; VanHouten, Joshua N et al. (2014) The remarkable migration of the medial collateral ligament. J Anat 224:490-8

Showing the most recent 10 out of 127 publications