Gli2 activator function in preosteoblasts is sufficient to mediate Ihh-dependent osteoblast differentiation, whereas the repressor function of Gli2 is dispensable for endochondral ossification

Developmental Dynamics

Volumn 239, Issue 6, 2010, Pages 1818-1826

  Kesper, Dörthe Andrea ^a   Didt Koziel, Lydia ^a   Vortkamp, Andrea ^a  

^a UNIVERSITY OF DUISBURG ESSEN   (Germany)

Author keywords

Bone; Cartilage; Gli2; Gli3; Indian hedgehog (Ihh); Ossification; Osteoblast

Indexed keywords

PROTEIN PATCHED 1; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI2; TRANSCRIPTION FACTOR GLI3; GLI1 PROTEIN, HUMAN; PROTEIN; REPRESSOR PROTEIN; TRANSCRIPTION FACTOR;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BONE TISSUE; CARTILAGE CELL; CELL DIFFERENTIATION; CONTROLLED STUDY; ENCHONDRAL OSSIFICATION; GENE ACTIVATION; GENE DELETION; GENE REPRESSION; GENE TARGETING; MESENCHYME; MOUSE; NONHUMAN; OSTEOBLAST; PERICHONDRIUM; PRIORITY JOURNAL; ANIMAL; ANIMAL EMBRYO; BONE DEVELOPMENT; FEMALE; GENETICS; METABOLISM; MUTANT MOUSE STRAIN; PHYSIOLOGY; PREGNANCY; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ERINACEIDAE;

ANIMALS; CELL DIFFERENTIATION; CHONDROCYTES; EMBRYO, MAMMALIAN; FEMALE; MICE; MICE, MUTANT STRAINS; MICE, TRANSGENIC; OSTEOBLASTS; OSTEOGENESIS; PREGNANCY; PROTEINS; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 77952694192     PISSN: 10588388     EISSN: 10970177     Source Type: Journal    
DOI: 10.1002/dvdy.22301     Document Type: Article

References (36)

1. Aza-Blanc P, Ramirez-Weber FA, Laget MP, Schwartz C, Kornberg TB. 1997. Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 89:1043-1053. (Pubitemid 127678738)
2. Aza-Blanc P, Lin HY, Ruiz i Altaba A, Kornberg TB. 2000. Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities. Development 127:4293-4301.
3. Bai CB, Joyner AL. 2001. Gli1 can rescue the in vivo function of Gli2. Development 128:5161-5172.
4. Bai CB, Stephen D, Joyner AL. 2004. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell 6:103-115. (Pubitemid 38089209)
5. Buttitta L, Mo R, Hui CC, Fan CM. 2003. Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction. Development 130:6233-6243. (Pubitemid 38008822)
6. Chen Y, Gallaher N, Goodman RH, Smolik SM. 1998. Protein kinase A directly regulates the activity and proteolysis of cubitus interruptus. Proc Natl Acad Sci USA 95:2349-2354. (Pubitemid 28145944)
7. Corrales JD, Blaess S, Mahoney EM, Joyner AL. 2006. The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation. Development 133:1811-1821. (Pubitemid 43810987)
8. Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP. 1996. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10:301-312. (Pubitemid 26058963)
9. Haigh JJ, Gerber HP, Ferrara N, Wagner EF. 2000. Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state. Development 127:1445-1453. (Pubitemid 30232595)
10. Hilton MJ, Tu X, Cook J, Hu H, Long F. 2005. Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development. Development 132:4339-4351. (Pubitemid 41576695)
11. Hu MC, Mo R, Bhella S, Wilson CW, Chuang PT, Hui CC, Rosenblum ND. 2006. GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development 133:569-578. (Pubitemid 43273842)
12. Hui CC, Joyner AL. 1993. A mouse model of Greig cephalopolysyndactyly syndrome: the extra-toes J mutation contains an intragenic deletion of the Gli3 gene. Nat Genet 3:241-246.
13. Hui CC, Slusarski D, Platt KA, Holmgren R, Joyner AL. 1994. Expression of three mouse homologs of the Drosophila segment polarity gene cubitus interruptus, Gli, Gli-2, and Gli-3, in ectoderm- and mesoderm-derived tissues suggests multiple roles during postimplantation development. Dev Biol 162:402-413. (Pubitemid 124002216)
14. Joeng KS, Long F. 2009. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development 136:4177-4185.
15. Karlstrom RO, Tyurina OV, Kawakami A, Nishioka N, Talbot WS, Sasaki H, Schier AF. 2003. Genetic analysis of zebrafish gli1 and gli2 reveals divergent requirements for Gli genes in vertebrate development. Development 130:1549-1564. (Pubitemid 36527516)
16. Koziel L, Wuelling M, Schneider S, Vortkamp A. 2005. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development 132:5249-5260. (Pubitemid 43020179)
17. Kronenberg HM. 2007. The role of the perichondrium in fetal bone development. Ann NY Acad Sci 1116:59-64. (Pubitemid 350274341)
18. Lei Q, Zelman AK, Kuang E, Li S, Matise MP. 2004. Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord. Development 131:3593-3604. (Pubitemid 39199369)
19. Litingtung Y, Chiang C. 2000. Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3. Nat Neurosci 3:979-985.
20. Litingtung Y, Dahn RD, Li Y, Fallon JF, Chiang C. 2002. Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature 418:979-983. (Pubitemid 34976033)
21. Logan M, Martin JF, Nagy A, Lobe C, Olson EN, Tabin CJ. 2002. Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 33:77-80. (Pubitemid 34651279)
22. Long F, Zhang XM, Karp S, Yang Y, McMahon AP. 2001. Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development 128:5099-5108. (Pubitemid 34086893)
23. Long F, Chung UI, Ohba S, McMahon J, Kronenberg HM, McMahon AP. 2004. Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development 131:1309-1318. (Pubitemid 38443885)
24. Mau E, Whetstone H, Yu C, Hopyan S, Wunder JS, Alman BA. 2007. PTHrP regulates growth plate chondrocyte differentiation and proliferation in a Gli3 dependent manner utilizing hedgehog ligand dependent and independent mechanisms. Dev Biol 305:28-39. (Pubitemid 46589405)
25. Methot N, Basler K. 2001. An absolute requirement for Cubitus interruptus in Hedgehog signaling. Development 128:733-742. (Pubitemid 32229250)
26. Mill P, Mo R, Fu H, Grachtchouk M, Kim PC, Dlugosz AA, Hui CC. 2003. Sonic hedgehog-dependent activation of Gli2 is essential for embryonic hair follicle development. Genes Dev 17:282-294. (Pubitemid 36105899)
27. Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A. 2002. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell 3:439-449.
28. Mo R, Freer AM, Zinyk DL, Crackower MA, Michaud J, Heng HH, Chik KW, Shi XM, Tsui LC, Cheng SH, Joyner AL, Hui C. 1997. Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development. Development 124:113-123. (Pubitemid 27053011)
29. Niedermaier M, Schwabe GC, Fees S, Helmrich A, Brieske N, Seemann P, Hecht J, Seitz V, Stricker S, Leschik G, Schrock E, Selby PB, Mundlos S. 2005. An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression. J Clin Invest 115:900-909. (Pubitemid 40489394)
30. Pan Y, Bai CB, Joyner AL, Wang B. 2006. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol 26:3365-3377.
31. Pan Y, Wang C, Wang B. 2009. Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development. Dev Biol 326:177-189.
32. Rice DP, Kim HJ, Thesleff I. 1999. Apoptosis in murine calvarial bone and suture development. Eur J Oral Sci 107:265-275.
33. Shimoyama A, Wada M, Ikeda F, Hata K, Matsubara T, Nifuji A, Noda M, Amano K, Yamaguchi A, Nishimura R, Yoneda T. 2007. Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function. Mol Biol Cell 18:2411-2418. (Pubitemid 47025707)
34. St-Jacques B, Hammerschmidt M, McMahon AP. 1999. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 13:2072-2086. (Pubitemid 29407348)
35. Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ. 1996. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613-622. (Pubitemid 26262108)
36. Young MF, Ibaraki K, Kerr JM, Lyu MS, Kozak CA. 1994. Murine bone sialoprotein (BSP): cDNA cloning, mRNA expression, and genetic mapping. Mamm Genome 5:108-111. (Pubitemid 2051288)