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Otx gene8/6/2023 Heterozygous mutations, including chromosomal deletions that span the OTX2 gene, have been implicated in major developmental malformations related to the eye. In humans, mutations in OTX2 have been described in patients with eye defects and variable congenital hypopituitarism (CH), ranging from isolated growth hormone deficiency (IGHD) ( 12) to combined pituitary hormone deficiency (CPHD) with/without an ectopic posterior pituitary (EPP) ( 6, 13, 14, 15, 16, 17). Furthermore, mice elicit a hypogonadotropic hypogonadism phenotype when Otx2 is conditionally knocked out in GnRH neurons ( 11). Neither of the latter two mutants, however, affect differentiation into the five specialized anterior pituitary cell types ( 3). Conditional knockout in the neural ectoderm (prospective posterior pituitary) results in a hypoplastic anterior lobe, posterior lobe and pituitary stalk, with loss of FGF signalling, which impairs anterior lobe growth. Conditional knockout of Otx2 in the retina leads to a failure in photoreceptor development ( 10), while conditional knockout of Otx2 with Foxg1-cre in limited brain regions and the oral ectoderm (the prospective anterior pituitary) causes craniofacial defects with abnormal pituitary gland morphology. Loss of murine Otx2 function due to a homozygous genetic mutation is associated with embryonic lethality due to complete loss of the forebrain, whilst heterozygous Otx2 mutant mice manifest a variable phenotype ranging from no obvious craniofacial anomaly to having microphthalmia/anophthalmia, otocephaly/micrognathia, and even acephaly in extreme cases ( 7, 8, 9). It is also important for the regulation of other transcription factors, such as Hesx1, which is essential for forebrain, pituitary and eye development ( 5, 6). The transcription factor orthodenticle protein homologue 2 (Otx2/OTX2) plays a distinct role in the patterning of the anterior neuroectoderm, midbrain, forebrain, pituitary gland and sensory organs including the inner ear, the pineal gland, and the eye (namely the optic nerves and retinal photoreceptors) ( 1, 2, 3, 4).
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