China 
Africa 
Explore chapters and articles related to this topic
Modeling Neuroretinal Development and Disease in Stem Cells
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Photoreceptor development is controlled by several different types of transcription factors. The homeodomain transcription factor orthodenticle homeobox 2 (Otx2) is an early factor that biases progenitor cells to become photoreceptors: conditional deletion of Otx2 leads to loss of photoreceptors; retroviral gene transfer of Otx2 into retinal progenitors promotes the photoreceptor fate (Nishida et al., 2003). Otx2 also activates the transcription of CRX (Furukawa et al., 1997), which is also required for the expression of photoreceptor-specific genes, including the opsins. In mice lacking Crx, photoreceptor cells do differentiate but completely fail to mature and eventually undergo apoptosis. Blimp1, a third critical and newly identified factor (Brzezinski et al., 2010) in mice, is shown to critically bias photoreceptor fate over bipolar cell fate during development. In mice with conditional Blimp1 deletion, there is a reduction in photoreceptor formation with a corresponding increase in differentiation of bipolar cells in the inner retina. Blimp1 has been shown to specifically repress VSX2 expression, which is required for the bipolar cell fate by binding to the enhancer region of VSX2 and blocking its activity (Katoh et al., 2010). A cis-regulatory element, B108, has recently been described as critical for Blimp1 expression and function (Wang et al., 2014). Otx2 and retinoic acid-related orphan receptor β (RORβ) regulate Blimp1 expression via B108. Additionally, the studies show that Blimp1 and Otx2 formed a negative feedback loop that regulates the level of Otx2, which in turn regulates the production of the correct ratio of rods and bipolar cells.
Parental occupational pesticide exposure and nonsyndromic orofacial clefts
Published in Journal of Occupational and Environmental Hygiene, 2018
Jonathan Suhl, Paul A. Romitti, Carissa Rocheleau, Yanyan Cao, Trudy L. Burns, Kristin Conway, Erin M. Bell, Patricia Stewart, Peter Langlois
Although the teratogenicity of prenatal pesticide exposure for OFCs has been demonstrated in several animal studies,[6–11] mechanisms by which pesticides affect lip and palate development are not well understood. Pesticides may mediate alterations to retinoic acid (RA) signaling in the developing embryo; RA affects proliferation and differentiation of cranial neural crest cells,[31] which give rise to the lip and palate.[32] Notably, expression of some genes, including Sonic hedgehog (Shh)[33] and Msx2,[34] mediated by RA and involved in lip and palate development were downregulated in rat embryos exposed to the fungicide, Triadimefon.[35] This fungicide also was shown to inhibit activity of RA degrading enzymes, leading to downregulation of transforming growth factor beta 1 (TGFB1) and TGFB2 expression in rats;[36]TGFB1, TGFB2 are involved in the reorientation and fusion of the palatal shelves.[reviewed in 4] Additionally, glyphosate-based herbicides were found to alter RA signaling in African clawed frog embryos, leading to elevated blood levels of RA[37] and subsequent down-regulation of Shh and Orthodenticle homeobox 2 (Otx2) genes and disruption of cranial neural crest cell development. The role of RA in disrupting neural crest cell development was further supported by prevention of craniofacial defects through resumption of normal Shh expression following administration of an RA antagonist.[37]