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PMID:16935278

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Citation

Young, B, Minugh-Purvis, N, Shimo, T, St-Jacques, B, Iwamoto, M, Enomoto-Iwamoto, M, Koyama, E and Pacifici, M (2006) Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. Dev. Biol. 299:272-82

Abstract

The synchondroses consist of mirror-image growth plates and are critical for cranial base elongation, but relatively little is known about their formation and regulation. Here we show that synchondrosis development is abnormal in Indian hedgehog-null mice. The Ihh(-/-) cranial bases displayed reduced growth and chondrocyte proliferation, but chondrocyte hypertrophy was widespread. Rather than forming a typical narrow zone, Ihh(-/-) hypertrophic chondrocytes occupied an elongated central portion of each growth plate and were flanked by immature collagen II-expressing chondrocytes facing perichondrial tissues. Endochondral ossification was delayed in much of the Ihh(-/-) cranial bases but, surprisingly, was unaffected most posteriorly. Searching for an explanation, we found that notochord remnants near incipient spheno-occipital synchondroses at E13.5 expressed Sonic hedgehog and local chondrocytes expressed Patched, suggesting that Shh had sustained chondrocyte maturation and occipital ossification. Equally unexpected, Ihh(-/-) growth plates stained poorly with Alcian blue and contained low aggrecan transcript levels. A comparable difference was seen in cultured wild-type versus Ihh(-/-) synchondrosis chondrocytes. Treatment with exogenous Ihh did not fully restore normal proteoglycan levels in mutant cultures, but a combination of Ihh and BMP-2 did. In summary, Ihh is required for multiple processes during synchondrosis and cranial base development, including growth plate zone organization, chondrocyte orientation, and proteoglycan production. The cranial base appears to be a skeletal structure in which growth and ossification patterns along its antero-posterior axis are orchestrated by both Ihh and Shh.

Links

PubMed Online version:10.1016/j.ydbio.2006.07.028

Keywords

Aggrecans/genetics; Animals; Cell Proliferation; Cells, Cultured; Chondrocytes/cytology; Chondrocytes/pathology; Chondrogenesis/physiology; Gene Expression Regulation, Developmental; Genetic Markers; Growth Plate/cytology; Growth Plate/embryology; Growth Plate/metabolism; Hedgehog Proteins/metabolism; Hypertrophy; Intracellular Signaling Peptides and Proteins/deficiency; Intracellular Signaling Peptides and Proteins/metabolism; Mice; Occipital Lobe/cytology; Osteogenesis/physiology; RNA, Messenger/genetics; RNA, Messenger/metabolism; Skull Base/cytology; Skull Base/embryology; Skull Base/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IHH

acts_upstream_of_or_within

GO:0006029: proteoglycan metabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88177
MGI:MGI:88177

P

Seeded From UniProt

complete

MOUSE:IHH

acts_upstream_of_or_within

GO:0060323: head morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1934258

P

Seeded From UniProt

complete

MOUSE:IHH

acts_upstream_of_or_within

GO:0035988: chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1934258

P

Seeded From UniProt

complete

MOUSE:BMP2

acts_upstream_of_or_within

GO:0006029: proteoglycan metabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96533
MGI:MGI:96533

P

Seeded From UniProt

complete


See also

References

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