A genomic atlas of mouse hypothalamic development

RIKEN-BSI, 2-1 Hirosawa, Wako-shi, Saitama, Japan.
Nature Neuroscience (Impact Factor: 16.1). 06/2010; 13(6):767-75. DOI: 10.1038/nn.2545
Source: PubMed


The hypothalamus is a central regulator of many behaviors that are essential for survival, such as temperature regulation, food intake and circadian rhythms. However, the molecular pathways that mediate hypothalamic development are largely unknown. To identify genes expressed in developing mouse hypothalamus, we performed microarray analysis at 12 different developmental time points. We then conducted developmental in situ hybridization for 1,045 genes that were dynamically expressed over the course of hypothalamic neurogenesis. We identified markers that stably labeled each major hypothalamic nucleus over the entire course of neurogenesis and constructed a detailed molecular atlas of the developing hypothalamus. As a proof of concept of the utility of these data, we used these markers to analyze the phenotype of mice in which Sonic Hedgehog (Shh) was selectively deleted from hypothalamic neuroepithelium and found that Shh is essential for anterior hypothalamic patterning. Our results serve as a resource for functional investigations of hypothalamic development, connectivity, physiology and dysfunction.

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    • "fferentially specified by a number of genes . These molecular subdivisions probably underpin causally the development of particular nuclei within these areas . Most of the genes studied code DNA - binding proteins , which probably are involved in fate and identity specification . These observations in general agree with additional data reported by Shimogori et al . ( 2010 ) , Diez - Roux et al . ( 2011 ) and Puelles et al . ( 2012 ) . While in most cases the observed restricted expression domains were limited to a single longitudinal zone , in the cases of Rgs4 and Plagl1 a large part of the basal plate area , including the TuI / RTuI , PM / PRM , and M / RM domains was neatly divided into THy and PHy mo"
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    Frontiers in Neuroanatomy 04/2015; 9:46. DOI:10.3389/fnana.2015.00046 · 3.54 Impact Factor
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    • "We observed that a significant fraction (5-10%) of hPSC-derived cells expressed these markers when directed to a hypothalamic identity, but not in control telencephalic differentiations (Fig. 4F). This efficiency is consistent with the expression of these factors in subsets of hypothalamic progenitors in the mouse brain (Acampora et al., 1999; Furukawa et al., 1997; Mathers et al., 1997; Shimogori et al., 2010; Simeone et al., 1994). We observed the most efficient induction of hypothalamic markers when we treated cultures with a combination of 1 μM Pur and 1 μM SAG from D2-8 (supplementary material Fig. S5). "
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    Development 02/2015; 142(4):633-43. DOI:10.1242/dev.117978 · 6.46 Impact Factor
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    • "In situ hybridization was performed as previously described (Shimogori et al, 2010). Full methods are described in Supplementary Information. "
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