Kohwi Minoree, Petryniak Magdalena A, Long Jason E, Ekker Marc, Obata Kunihiko, Yanagawa Yuchio, Rubenstein John L R, Alvarez-Buylla Arturo
Department of Neurosurgery, University of California at San Francisco, San Francisco, California 94143, USA.
J Neurosci. 2007 Jun 27;27(26):6878-91. doi: 10.1523/JNEUROSCI.0254-07.2007.
The subventricular zone (SVZ) of the postnatal brain continuously generates olfactory bulb (OB) interneurons. We show that calretinin+, calbindin+, and dopaminergic (TH+) periglomerular OB interneurons correspond to distinct subtypes of GABAergic cells; all were produced in the postnatal mouse brain, but they matured and were eliminated at different rates. The embryonic lateral ganglionic eminence (LGE) is thought to be the site of origin of postnatal SVZ neural progenitors. Consistently, grafts of the embryonic LGE into the adult brain SVZ generated many OB interneurons, including TH+ and calbindin+ periglomerular interneurons. However, calretinin+ cells were not produced from these LGE grafts. Surprisingly, pallial and septal embryonic progenitors transplanted into the adult brain SVZ also resulted in the generation of OB interneurons, including calretinin+ cells. A subset of Dlx2+ OB interneurons was derived from cells expressing Emx1, a transcription factor largely restricted to the pallium during development. Emx1 lineage-derived cells contributed a substantial portion of GABAergic cells in the OB, including calretinin+ interneurons. This is in contrast to cortex, in which Emx1 lineage-derived cells do not differentiate into GABAergic neurons. Our results suggest that some OB interneurons are derived from progenitors outside the LGE and that precursors expressing what has classically been considered a pallial transcription factor generate GABAergic interneurons.
出生后大脑的脑室下区(SVZ)持续产生嗅球(OB)中间神经元。我们发现,钙视网膜蛋白阳性、钙结合蛋白阳性和多巴胺能(TH阳性)的球周OB中间神经元对应于不同亚型的GABA能细胞;它们均在出生后的小鼠大脑中产生,但成熟和被清除的速率不同。胚胎期的外侧神经节隆起(LGE)被认为是出生后SVZ神经祖细胞的起源部位。一致的是,将胚胎LGE移植到成年大脑的SVZ中可产生许多OB中间神经元,包括TH阳性和钙结合蛋白阳性的球周中间神经元。然而,这些LGE移植并未产生钙视网膜蛋白阳性细胞。令人惊讶的是,移植到成年大脑SVZ中的皮质和隔区胚胎祖细胞也导致了OB中间神经元的产生,包括钙视网膜蛋白阳性细胞。一部分Dlx2阳性的OB中间神经元来源于表达Emx1的细胞,Emx1是一种在发育过程中主要局限于皮质的转录因子。Emx1谱系来源的细胞在OB中贡献了很大一部分GABA能细胞,包括钙视网膜蛋白阳性中间神经元。这与皮质不同,在皮质中,Emx1谱系来源的细胞不会分化为GABA能神经元。我们的结果表明,一些OB中间神经元来源于LGE之外的祖细胞,并且表达传统上被认为是皮质转录因子的前体细胞可产生GABA能中间神经元。