The hedgehog pathway and ocular developmental anomalies

Abstract

Mutations in effectors of the hedgehog signaling pathway are responsible for a wide variety of ocular developmental anomalies. These range from massive malformations of the brain and ocular primordia, not always compatible with postnatal life, to subtle but damaging functional effects on specific eye components. This review will concentrate on the effects and effectors of the major vertebrate hedgehog ligand for eye and brain formation, Sonic hedgehog (SHH), in tissues that constitute the eye directly and also in those tissues that exert indirect influence on eye formation. After a brief overview of human eye development, the many roles of the SHH signaling pathway during both early and later morphogenetic processes in the brain and then eye and periocular primordia will be evoked. Some of the unique molecular biology of this pathway in vertebrates, particularly ciliary signal transduction, will also be broached within this developmental cellular context.

Pituitary stalk interruption syndrome broadens the clinical spectrum of the TTC26 ciliopathy

“…Many syndromic ciliopathies display ocular findings, such as, strabismus, retinal involvement, microphthalmia and coloboma, as part of their phenotypic spectrum, emphasizing the importance of intact ciliary function for ocular development 18 . Like PSIS, microphthalmia and coloboma are part of the phenotypic spectrum of holoprosencephaly and are associated with defective SHH signaling 19 . Therefore, it seems reasonable that the ocular findings observed in our cohort represent part of the phenotype related to defective TTC26 .…”

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia

“…Given the critical role of the SHH pathway in eye morphogenesis (Cavodeassi et al 2018), PTCH1 involvement in ocular developmental defects would not be surprising. However, there have been no other reports of PTCH1 mutations in developmental eye anomalies.…”

The diverse neural crest: from embryology to human pathology

“…Likewise, forebrain, eye and pituitary growth all depend on the modulation of local inductive signals by the FSNC, as mentioned earlier (Creuzet, 2009;Etchevers et al, 1999;Evans and Gage, 2005). These tissues are sensitive to gene mutations that induce holoprosencephaly, which may be associated with cleft palate or outflow tract malformations (reviewed by Cavodeassi et al, 2018).…”