Transcription factors in glutamatergic neurogenesis: Conserved programs in neocortex, cerebellum, and adult hippocampus

Hevner, Robert F.; Hodge, Rebecca D.; Daza, Ray A. M.; Englund, Chris

doi:10.1016/j.neures.2006.03.004

Cited by 401 publications

(418 citation statements)

References 95 publications

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“…According to a current model of adult hippocampus neurogenesis, GFAP, Sox2, and Nestin expressing neural stem cells (type-1 cells) differentiate into neural progeni- tor cells expressing NeuroD and Dcx (type-2b or 3 cells). Previous reports place transcription factors, Tbr2 and Neurog2, in the type-2b or 3 cells as well, a stage after Ascl1 expression (Hevner et al, 2006;Ozen et al, 2007). Ascl1 is a unique marker for type-2a cells, and in particular it marks cells that are actively transitioning from progenitor to differentiated neuron.…”

Section: Discussionmentioning

confidence: 96%

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

et al. 2007

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In the adult mammalian brain, new neurons and glia are continuously generated but molecular factors regulating their differentiation and lineage relationships are largely unknown. We show that Ascl1, a bHLH (basic helix-loop-helix) transcription factor, transiently labels neuronal and oligodendrocyte precursors in the adult brain. Using in vivo lineage tracing with inducible Cre recombinase, we followed the maturation of these precursors in four distinct regions.

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Section: Discussionmentioning

confidence: 96%

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

et al. 2007

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“…Surprisingly, the Math1+ RL gives rise not only to glutamatergic granule neurons, but to all known glutamatergic neurons of the cerebellum. These include both unipolar brush cells, which serve as a relay cell amplifying the excitatory effects of mossy afferent fibers on granule cells [12], as well as the glutamateric subset of deep cerebellar nuclei neurons, [13][14][15][16][17][18] (Figure 1A). Thus, the well ordered cellular organization of the mature cerebellum is achieved through the bipartite origins of its constituent neurons.…”

Section: Distinct Origins For Gabaergic and Glutamatergic Cerebellar mentioning

confidence: 99%

“…Thus, the well ordered cellular organization of the mature cerebellum is achieved through the bipartite origins of its constituent neurons. Despite the complexity of the final mature structure, the cerebellum is not that different from the developing spinal cord and telencephalon, where distinctly ordered progenitors along the dorsal/ventral axis of the neural tube give rise to cells of distinct neurotransmitter phenotypes [18].…”

Section: Distinct Origins For Gabaergic and Glutamatergic Cerebellar mentioning

confidence: 99%

Cerebellar development and disease

Millen¹,

Gleeson²

2008

Current Opinion in Neurobiology

171

141

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The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitterspecific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum.

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“…7 Among these, Ngn2 is required for transition from early Pax6 þ radial glia to Tbr2 þ INPs, as well as for expansion of INPs, whereas NeuroD1 is expressed in INPs and early-differentiating neurons. 7,8 How their sequential timed expression is regulated to promote the development of normal-sized cortices is unknown.The development of human microcephaly likely results from abnormal cortical precursor behavior. Interestingly, deletion of the distal end of human chromosome-1q is linked to microcephaly with agenesis of the corpus callosum (e.g.…”

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confidence: 99%

mentioning

confidence: 99%

RP58/ZNF238 directly modulates proneurogenic gene levels and is required for neuronal differentiation and brain expansion

et al. 2011

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Although neurogenic pathways have been described in the developing neocortex, less is known about mechanisms ensuring correct neuronal differentiation thus also preventing tumor growth. We have shown that RP58 (aka zfp238 or znf238) is highly expressed in differentiating neurons, that its expression is lost or diminished in brain tumors, and that its reintroduction blocks their proliferation. Mice with loss of RP58 die at birth with neocortical defects. Using a novel conditional RP58 allele here we show that its CNS-specific loss yields a novel postnatal phenotype: microencephaly, agenesis of the corpus callosum and cerebellar hypoplasia that resembles the chr1qter deletion microcephaly syndrome in human. RP58 mutant brains maintain precursor pools but have reduced neuronal and increased glial differentiation. Well-timed downregulation of pax6, ngn2 and neuroD1 depends on RP58 mediated transcriptional repression, ngn2 and neuroD1 being direct targets. Thus, RP58 may act to favor neuronal differentiation and brain growth by coherently repressing multiple proneurogenic genes in a timely manner. The cerebral cortex undergoes rapid expansion during embryogenesis, when neuronal layers are formed. Two main types of precursors exist in the developing neocortex: multipotent radial glial stem/progenitor cells (RGCs) in the ventricular zone (VZ) and derived intermediate neurogenic progenitors (INPs) in the subventricular zone (SVZ). 1-3 INPs divide 1-2 times and only give rise to neurons, with regulation of their number proposed to contribute to cortical expansion. [1][2][3][4][5][6] Molecularly, a sequence of key transcription factors, Pax6-4Ngn2-4Tbr2-4NeuroD1-4Tbr1, promotes cortical neurogenesis. 7 Among these, Ngn2 is required for transition from early Pax6 þ radial glia to Tbr2 þ INPs, as well as for expansion of INPs, whereas NeuroD1 is expressed in INPs and early-differentiating neurons. 7,8 How their sequential timed expression is regulated to promote the development of normal-sized cortices is unknown.The development of human microcephaly likely results from abnormal cortical precursor behavior. Interestingly, deletion of the distal end of human chromosome-1q is linked to microcephaly with agenesis of the corpus callosum (e.g. 9-11), and a critical region contains only a handful of genes, including RP58. 9-12 RP58, also known as ZNF238, 13 encodes a transcription factor with a BTB/POZ and four zincfinger domains 14 that is highly conserved (495%) between humans and mice, suggesting conserved functions.Previous work has shown that RP58 is expressed in mouse brain precursors and neurons, 15 and that its complete loss leads to defects in cortical and hippocampal development. 16 Critically, perinatal death of conventional knockout (KO) mice 16 precludes analyses in postnatal stages. Furthermore, the reported defects in cell-cycle exit, and in Pax6 þ and Tbr2 þ populations, were deduced from analyses at late corticogenesis stages after embryonic day (E) 16.5, precluding any conclusions on early defects and not provi...

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Transcription factors in glutamatergic neurogenesis: Conserved programs in neocortex, cerebellum, and adult hippocampus

Cited by 401 publications

References 95 publications

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

In VivoAnalysis of Ascl1 Defined Progenitors Reveals Distinct Developmental Dynamics during Adult Neurogenesis and Gliogenesis

Cerebellar development and disease

RP58/ZNF238 directly modulates proneurogenic gene levels and is required for neuronal differentiation and brain expansion

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