scholarly journals Forebrain patterning defects in Small eye mutant mice

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3453-3465 ◽  
Author(s):  
A. Stoykova ◽  
R. Fritsch ◽  
C. Walther ◽  
P. Gruss

Pax6 is a member of the Pax gene family of transcriptional regulators that exhibits a restricted spatiotemporal expression in the developing central nervous system, eye and nose. Mutations in Pax6 are responsible for inherited malformations in man, rat and mouse. To evaluate the role of Pax6 in forebrain development, we studied in detail mouse Small eye/Pax6 mutant brains. This analysis revealed severe defects in forebrain regions where Pax6 is specifically expressed. The establishment of some expression boundaries along the dorsoventral axis of the secondary prosencephalon is distorted and the specification of several ventral structures and nuclei is abolished. Specifically, the development of the hypothalamo-telencephalic transition zone and the ventral thalamus is distorted. Our detailed analysis included a comparison of the expression of Pax6, Dlx1 and several other genes during embryonic mouse brain development in wild-type and in the mutant Small eye (Sey) brain. The results from the analysis of normal brain development show that the restricted expression of Pax6 and Dlx1 at E12.5 dpc respect domains within the forebrain, consistent with the implications of the prosomeric model for the organisation of the forebrain (L. Puelles and J. L. R. Rubenstein (1993) Trends Neurosci. 16, 472–479). Furthermore, we found an early restriction of Pax6 and Dlx1 expression into presumptive histogenetic fields that correlate with the formation of distinct forebrain structures and nuclei. Our results are discussed in light of changes in adhesive properties in the Sey brain that might control segregation, assembly and cell migration of progenitors of specific forebrain regions.


Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.





2007 ◽  
Vol 13 (6) ◽  
pp. 1072-1073
Author(s):  
Doug Johnson-Greene

Brain Development: Normal Processes and the Effects of Alcohol and Nicotine. Michael W. Miller (Ed.). 2006. New York: Oxford University Press, 424 pp., $98.50 (HB)The process of brain development is an essential yet often overlooked area in the neuropsychological literature. The topic has a natural appeal to those who work with children where developmental disorders predominate. However, it is often more difficult for those who work with adults to appreciate the role of developmental aberrations and their contribution to pathological processes that may seem far removed from the early developmental history of our patients. The tendency for some to deemphasize early developmental influences may stem in part from a lack of clarity about how common toxin exposures, such as alcohol and nicotine, alter normal brain development and contribute to changes in cognitive function. Increasingly, evidence of early developmental influences has emerged in a host of epigenetically-based developmental disorders and neuropathological conditions, such as schizophrenia, and these influences are also implicated in theoretical models, such as cognitive reserve.



NeuroImage ◽  
2016 ◽  
Vol 124 ◽  
pp. 1125-1130 ◽  
Author(s):  
Lindsay Walker ◽  
Lin-Ching Chang ◽  
Amritha Nayak ◽  
M. Okan Irfanoglu ◽  
Kelly N. Botteron ◽  
...  


2008 ◽  
Vol 2 (Suppl 1) ◽  
pp. P61
Author(s):  
Chelsea M Ruller ◽  
Jenna M Tabor-Godwin ◽  
Scott Robinson ◽  
Naili An ◽  
J Lindsay Whitton ◽  
...  




2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi188-vi188
Author(s):  
Nourhan Abdelfattah ◽  
Sivaraman Natarajan ◽  
Yaohui Chen ◽  
Kin-Hoe Chow ◽  
Shu-hsia Chen ◽  
...  

Abstract Immunotherapies offer remarkable potential to provide robust therapeutic benefit. Patients suffering from medulloblastoma (MB), the most frequent pediatric brain malignancy, can especially benefit from this approach, minimizing the devastating side effects of aggressive radiation and chemotherapies that disrupt normal brain development. However, regulators of the immune landscape remain poorly understood and no effective immunotherapies exist yet for MB. Here, we describe a sex-dependent Yap1 function in fSmoM2;GFAPcre SHH-MB (SG) mouse model. We show that Yap1 is both a cell-autonomous regulator of MB stem-cells and a non-cell-autonomous regulator of immune infiltrates in SHH-MB. Yap1 deletion in SG mice results in increased neuronal differentiation, significantly extended survival, and enhanced infiltration of peripheral blood immune cells (including cytotoxic T-cells, neutrophils, and macrophages). Additionally, this rescue phenotype is observed in a sex-biased manner: 65% of Yap1f/f;fSmoM2;GFAPcre males are rescued in contrast to 35% of females. These observations implicate Yap1 as a mediator of sex-biased brain-tumor formation, either through direct modulation of MB cells and/or through indirectly mediating the MB immune landscape. We are currently testing the role of sex-specific differences in the developing mouse brain to elucidate context-dependent function of Yap1 in MB genesis and maintenance.



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