Abstract
The subpallium comprises large parts of the basal ganglia including striatum and globus pallidus. Genes and factors involved in the development of the subpallium have been extensively studied in most vertebrates, including amphibians, birds, and rodents. However, our knowledge on patterning of the human subpallium remains insufficient. Using double fluorescent immunohistochemistry, we investigated the protein distribution of transcription factors involved in patterning of the subventricular zone (SVZ) in the human forebrain at late embryonic development. Furthermore, we compared the development of cortical and striatal precursors between human fetal brain and E14 and E16 fetal rat brains. Our results reveal that DLX2 marks SVZ precursors in the entire subpallium. Individual subpallial subdomains can be identified based on co-expression of DLX2 with either PAX6 or NKX2-1. SVZ precursors in the dorsal LGE and preopto-hypothalamic boundary are characterized by DLX2/PAX6 co-expression, while precursors in the MGE and preoptic region co-express DLX2/NKX2-1. SVZ precursors in the ventral LGE are DLX2(+)/PAX6(-)/NKX2-1(-). In terms of staging comparisons, the development of the corpus striatum in the human fetal brain during late embryonic stages corresponds well with the development of the striatum observed in E14 fetal rat brains. Our study demonstrates that the pattern underlying the development of the subpallium is highly conserved between rodents and humans and suggests a similar function for these factors in human brain development. Moreover, our data directly influence the application of ganglionic eminence derived human tissue for cell therapeutic approaches in neurodegenerative disorders such as Huntington's disease.
Highlights
During embryonic development, the future forebrain is already determined by expression of OTX2 in the neuroectoderm at the gastrula stage (Simeone et al, 1993)
We investigated the protein distribution of transcription factors involved in patterning of the subventricular zone (SVZ) in the human forebrain at late embryonic development
MGE and preoptic region (PO) are characterized by the co-localization of DLX2 and NKX21, while the dorsal-most part of the LGE and the POH can be identified based on DLX2 and PAX6 co-localization as well as by the lack of NKX2-1 expression
Summary
The future forebrain is already determined by expression of OTX2 in the neuroectoderm at the gastrula stage (Simeone et al, 1993). The neural tube is divided into four longitudinal zones along the dorsoventral axis (floor, basal, alar, and roof plate). The anterior part of the neural tube that will develop into the encephalon is divided into initially three transverse zones along the anterior-posterior axis: the anterior prosencephalon (forebrain), the mesencephalon (midbrain), and the posterior rhombencephalon (hindbrain). Our knowledge of mechanisms involved in controlling neural progenitor region patterning and brain development is almost completely derived from animal models. In contrast to earlier distinctions which were solely based on anatomic landmarks, the current widely accepted model of the prosencephalic subdivision provided by (Puelles and Rubenstein, 2003) relies on gene expression patterns of transcription factors (mainly of DLX, NKX, LHX, and PAX family members) in subventricular zone (SVZ)
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