Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function

Blanche Young, Nancy Minugh-Purvis, Tsuyoshi Shimo, Benoit St-Jacques, Masahiro Iwamoto, Motomi Enomoto-Iwamoto, Eiki Koyama, Maurizio Pacifici

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)272-282
Number of pages11
JournalDevelopmental Biology
Volume299
Issue number1
DOIs
Publication statusPublished - Nov 1 2006

Fingerprint

Growth Plate
Hedgehogs
Skull Base
Chondrocytes
Osteogenesis
Proteoglycans
Notochord
Aggrecans
Alcian Blue
Growth
Hypertrophy
Collagen

Keywords

  • Aggrecan
  • BMPs
  • Cranial base
  • Extracellular matrix
  • Growth plate
  • Indian hedgehog
  • Skeletogenesis
  • Sonic hedgehog
  • Synchondrosis

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Young, B., Minugh-Purvis, N., Shimo, T., St-Jacques, B., Iwamoto, M., Enomoto-Iwamoto, M., ... Pacifici, M. (2006). Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. Developmental Biology, 299(1), 272-282. https://doi.org/10.1016/j.ydbio.2006.07.028

Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. / Young, Blanche; Minugh-Purvis, Nancy; Shimo, Tsuyoshi; St-Jacques, Benoit; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Pacifici, Maurizio.

In: Developmental Biology, Vol. 299, No. 1, 01.11.2006, p. 272-282.

Research output: Contribution to journalArticle

Young, B, Minugh-Purvis, N, Shimo, T, St-Jacques, B, Iwamoto, M, Enomoto-Iwamoto, M, Koyama, E & Pacifici, M 2006, 'Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function', Developmental Biology, vol. 299, no. 1, pp. 272-282. https://doi.org/10.1016/j.ydbio.2006.07.028
Young B, Minugh-Purvis N, Shimo T, St-Jacques B, Iwamoto M, Enomoto-Iwamoto M et al. Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. Developmental Biology. 2006 Nov 1;299(1):272-282. https://doi.org/10.1016/j.ydbio.2006.07.028
Young, Blanche ; Minugh-Purvis, Nancy ; Shimo, Tsuyoshi ; St-Jacques, Benoit ; Iwamoto, Masahiro ; Enomoto-Iwamoto, Motomi ; Koyama, Eiki ; Pacifici, Maurizio. / Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. In: Developmental Biology. 2006 ; Vol. 299, No. 1. pp. 272-282.
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