The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes
The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular fact...
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doaj-635bae69b61c41a8a437e1acb96321cc2021-09-26T00:23:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-01229854985410.3390/ijms22189854The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly SyndromesChristine K. C. Loo0Michael A. Pearen1Grant A. Ramm2South Eastern Area Laboratory Services, Department of Anatomical Pathology, NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW 2031, AustraliaHepatic Fibrosis Group, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, AustraliaHepatic Fibrosis Group, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, AustraliaThe Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. <i>SHH</i> mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed.https://www.mdpi.com/1422-0067/22/18/9854Sonic Hedgehoghuman holoprosencephalyshort-rib polydactyly syndromes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine K. C. Loo Michael A. Pearen Grant A. Ramm |
spellingShingle |
Christine K. C. Loo Michael A. Pearen Grant A. Ramm The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes International Journal of Molecular Sciences Sonic Hedgehog human holoprosencephaly short-rib polydactyly syndromes |
author_facet |
Christine K. C. Loo Michael A. Pearen Grant A. Ramm |
author_sort |
Christine K. C. Loo |
title |
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes |
title_short |
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes |
title_full |
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes |
title_fullStr |
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes |
title_full_unstemmed |
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes |
title_sort |
role of sonic hedgehog in human holoprosencephaly and short-rib polydactyly syndromes |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-09-01 |
description |
The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. <i>SHH</i> mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed. |
topic |
Sonic Hedgehog human holoprosencephaly short-rib polydactyly syndromes |
url |
https://www.mdpi.com/1422-0067/22/18/9854 |
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