We report the unprecedented finding that the conserved RNA-binding motif protein, RBM24, positively controls Sox2 mRNA stability and is necessary for optimal SOX2 mRNA and protein levels in development, perturbation of which causes ocular defects, including microphthalmia and anophthalmia.
Selective loss of neogenin in neural crest cells (as observed in Wnt1-Cre; Neof/f mice), but not neural stem cells (as observed in GFAP-Cre and Nestin-Cre; Neof/f mice), resulted in a dysregulation of neural crest cell migration or delamination, exhibiting features of PHPV-like pathology (e.g., elevated retrolental mass), unclosed retinal fissure, and microphthalmia.
Here we support the link between CDK5RAP2 and eye development by showing that most Cdk5rap2 mutant mice (an/an) exhibit eye malformations ranging from reduced size of one or both eyes (microphthalmia) to total absence of both eyes (anophthalmia).
<b>Conclusions</b>: We identified a novel missense mutation p.S93R in CRYBB1 in a Chinese family with autosomal dominant congenital cataracts and microphthalmia.
Selective loss of neogenin in neural crest cells (as observed in Wnt1-Cre; Neof/f mice), but not neural stem cells (as observed in GFAP-Cre and Nestin-Cre; Neof/f mice), resulted in a dysregulation of neural crest cell migration or delamination, exhibiting features of PHPV-like pathology (e.g., elevated retrolental mass), unclosed retinal fissure, and microphthalmia.
STTM‑miR‑143‑5p overexpression resulted in an increased expression of downstream melanogenesis genes including microphthalmia‑associated transcription factor (MITF), tyrosinase family members [tyrosinase (TYR) and tyrosinase‑related protein 1 (TYRP1)], melanophilin (MLPH), and Rab27a, thereby contributing to melanocyte pigmentation by promoting total alkali‑soluble melanogenesis (ASM) and eumelanin (EM) contents; conversely, STTM‑miR‑143‑5p overexpression resulted in decreased expression of the tyrosinase‑related protein 2 (TYRP2)/dopachrome tautomerase (DCT), which is responsible for decreased pheomelanin (PM) content in mouse melanocytes.
We concluded that: (1) CD13 and GATA-3 immunostains may serve as a diagnostic aid in differentiating subtypes of RCC; (2) CD13 is always absent in chromophobe RCC and oncocytomas, whereas CD10 can be immunoexpressed in both; (3) CD13 should be included in a panel of antibodies to distinguish "proximal renal tumors" from "distal renal tumors" and between clear cell RCC versus microphthalmia transcription factor family translocations RCCs; and (4) when present, GATA-3 is specific for clear cell papillary RCC.
High-throughput transcriptome analysis reveals that the loss of Pten activates a novel NKX6-1/RASGRP1 regulatory module to rescue microphthalmia caused by Fgfr2-deficient lenses.
We concluded that: (1) CD13 and GATA-3 immunostains may serve as a diagnostic aid in differentiating subtypes of RCC; (2) CD13 is always absent in chromophobe RCC and oncocytomas, whereas CD10 can be immunoexpressed in both; (3) CD13 should be included in a panel of antibodies to distinguish "proximal renal tumors" from "distal renal tumors" and between clear cell RCC versus microphthalmia transcription factor family translocations RCCs; and (4) when present, GATA-3 is specific for clear cell papillary RCC.
STTM‑miR‑143‑5p overexpression resulted in an increased expression of downstream melanogenesis genes including microphthalmia‑associated transcription factor (MITF), tyrosinase family members [tyrosinase (TYR) and tyrosinase‑related protein 1 (TYRP1)], melanophilin (MLPH), and Rab27a, thereby contributing to melanocyte pigmentation by promoting total alkali‑soluble melanogenesis (ASM) and eumelanin (EM) contents; conversely, STTM‑miR‑143‑5p overexpression resulted in decreased expression of the tyrosinase‑related protein 2 (TYRP2)/dopachrome tautomerase (DCT), which is responsible for decreased pheomelanin (PM) content in mouse melanocytes.
YME1L-deficient mice manifest ocular dysfunction with microphthalmia and cataracts and develop deficiencies in locomotor activity due to specific degeneration of spinal cord axons, which relay proprioceptive signals from the hind limbs to the cerebellum.
Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (<i>M</i><i>TORC1</i>) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited.
The loss of Lrp4 resulted in an elevated incidence of microphthalmia and affected the mRNA expression of the members of bone morphogenetic protein, fibroblast growth factor, Sonic hedgehog, and WNT signaling pathways and of several pathogenic genes for microphthalmia.
The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1).
Based on our findings, we propose that tight regulation of Crim1 activity is required for maintenance of the lens epithelium, and its depletion leads to ectopic differentiation into fiber cells, dramatically altering lens structure and ultimately leading to microphthalmia and aphakia.
The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1).
Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia.
In addition, resorcinol suppressed the expression of melanogenic gene microphthalmia-associated transcriptional factor (MITF) and its downstream target genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2.
Morpholino-oligonucleotide-induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient.
Here, STTM-miR508-3p overexpression in alpaca melanocytes blocked the expression of miR-508-3p and up-regulated SOX6 expression at both the mRNA and protein levels, resulting in increasing the expression of key melanogenic genes, including cAMP responsive element (CRE) binding protein (CREB), MITF, tyrosinase (TYR) and tyrosinase-related protein 1 and 2 (TYRP1 and TYRP2).
The membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; also, the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL.