Migration patterns of clonally related granule cells and their progenitors in the developing chick cerebellum

Ryder, Elizabeth F.; Cepko, Constance L.

doi:10.1016/0896-6273(94)90310-7

Cited by 143 publications

(107 citation statements)

References 42 publications

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“…What was surprising was our finding that some of these Math1-positive cells that originate from the ARL populate the cerebellum. The origins of all but the principal neurons of the cerebellum have been a subject of much debate (Hallonet et al, 1990;Alvarez Otero et al, 1993;Ryder and Cepko, 1994;Alder et al, 1996;Zhang and Goldman, 1996). The majority of studies addressing this issue finds that the EGL only gives rise to granule cells.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Jensen¹,

Smeyne²,

Goldowitz³

2004

J. Neurosci.

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The cerebellar granule cell is the most numerous neuron in the nervous system and likely the source of the most common childhood brain tumor, medulloblastoma. The earliest known gene to be expressed in the development of these cells is math1. In the math1 null mouse, neuroblasts never populate the external germinal layer (EGL) that gives rise to granule cells. In this study, we examined the embryonic development of the math1 null cerebellum and analyzed experimental mouse chimeras made from math1 null embryos. We find that the anterior rhombic lip gives rise to more than one cell type, indicating that the rhombic lip does not consist of a homogeneous population of cells. Furthermore, we demonstrate that math1 null granule cells are absent in the math1 null chimeric cerebellum, from the onset of their genesis in the mouse anterior rhombic lip. This finding indicates a vital cell intrinsic role for Math1 in the granule cell lineage. In addition, we show that wild-type cells are unable to compensate for the loss of mutant cells. Finally, the colonization of the EGL by wild-type cells and the presence of acellular gaps provides evidence that EGL neuroblasts undergo active migration and likely have a predetermined spatial address in the rhombic lip.

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Section: Discussionmentioning

confidence: 99%

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Jensen¹,

Smeyne²,

Goldowitz³

2004

J. Neurosci.

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“…There is a temporal relationship between the time when the gcps exit the rhombic lip and their final anterior-posterior (AP) position in the EGL, with the gcps that exit first (E13.5) residing more anteriorly than those that exit later (Machold and Fishell, 2005). Accordingly, early clonal marking of chick gcps leaving the rhombic lip produced clones that spread mainly along the AP axis and spanned many folia (Ryder and Cepko, 1994). However, gcp behaviors that govern foliation after establishment of the EGL, during the period of major cerebellar growth and fissure formation, remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum

2015

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The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.

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“…In particular, immature neurons generated in the EGL migrate along radial processes of glial cells through the molecular layer to reach their final destination within the internal granule cell layer (IGL) [19]. In vivo administration of PACAP at the surface of the cerebellum of 8-day-old rats increased cerebellar cortical volume [21], mainly through an increase in the number of granule cells in the IGL.…”

Section: Introductionmentioning

confidence: 99%

Endogenous PACAP acts as a stress response peptide to protect cerebellar neurons from ethanol or oxidative insult

et al. 2005

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The rodent cerebellum is richly supplied with PACAPergic innervation. Exogenous pituitary adenylate cyclase-activating polypeptide (PACAP) increases cerebellar granule cell survival and differentiation in culture, and enhances the number of neuroblasts in the molecular and internal granule cell layers (IGL) when injected postnatally into the cerebellum in vivo. Here, we have investigated the role of endogenous PACAP during cerebellar development by comparing the morphology of normal and PACAP-deficient mouse cerebellum, and the response of cerebellar granule cells from normal and PACAP-deficient mice subjected to neurotoxic insult in culture. There was no difference in cerebellar volume or granule cell number, in 11-day-old wild type versus PACAP-deficient mice. Cultured cerebellar neurons from PACAP-deficient and wild type mice also showed no apparent differences in survival and differentiation either under depolarizing conditions, or non-depolarizing conditions in the presence or absence of either dibutyryl cAMP or 100 nM PACAP. However, cultured cerebellar neurons from PACAP-deficient mice were significantly more sensitive than wild type neurons to ethanol-or hydrogen peroxide-induced toxicity. Differential ethanol toxicity was reversed by addition of 100 nM exogenous PACAP, suggesting that endogenous PACAP has neuroprotective activity in the context of cellular insult or stress. The neuroprotective action of PACAP was mimicked by dibutryl cAMP, indicating that it occurred via activation of adenylate cyclase. These results indicate that PACAP might act to protect the brain from paraphysiological insult, including exposure to toxins or hypoxia.

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Migration patterns of clonally related granule cells and their progenitors in the developing chick cerebellum

Cited by 143 publications

References 42 publications

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Analysis of Cerebellar Development inmath1Null Embryos and Chimeras

Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum

Endogenous PACAP acts as a stress response peptide to protect cerebellar neurons from ethanol or oxidative insult

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