Physiological Purkinje Cell Death Is Spatiotemporally Organized in the Developing Mouse Cerebellum

Abstract

Physiological cell death is crucial for matching defined cellular populations within the central nervous system. Whereas the time course of developmental cell death in the central nervous system is well analyzed, information about its precise spatial patterning is scarce. Yet, the latter one is needed to appraise its contribution to circuit formation and refinement. Here, we document that during normal cerebellar development, dying Purkinje cells were highly localized within the vermal midline and in a lobule specific, parasagittal pattern along the whole mediolateral axis. In addition, single hot spots of cell death localized to the caudal declive and ventral lobule IX within the posterolateral fissure. These hot spots of dying Purkinje cells partly overlapped with gaps within the Purkinje cell layer which supports the classification of different gaps based on histological and molecular criteria, i.e., midline gap, patchy gaps, and raphes. Areas characterized by a high incidence of Purkinje cell death and gaps colocalize with known molecular and functional boundaries within the cerebellar cortex. Physiological cell death can thus be considered to serve as an important regulator of cerebellar histogenesis.

Merlin Inhibits Neurite Outgrowth in the CNS

“…After vigorous washings, sections were incubated with the secondary antibody solution (Alexa Fluor 488-and Alexa Fluor 546-conjugated goat anti-mouse and anti-rabbit antibodies, 1:500 in PBS; Invitrogen) at room temperature for 2 h. Finally, sections were counterstained using Hoechst 34580 (1 g/ml PBS, 5 min), washed for at least 1 h, and embedded in Mowiol. Although calbindin and MBP immunohistochemical stainings are well established (BouslamaOueghlani et al, 2003;Jankowski et al, 2009), we checked for merlinspecific staining using several procedures. First, omitting the primary antibody revealed no signal; and second, incubating sections with a merlin-specific peptide (10-fold excess) diminished the specific binding to background levels (supplemental Fig.…”

Perseverative responding and neuroanatomical alterations in adult heterozygous reeler mice are mitigated by neonatal estrogen administration

“…Interestingly, Maloku et al (2010) have also found a similar PC loss in adult reelin-haploinsufficient mice, and have interpreted their findings in the context of reelin deficiency and cerebellar abnormalities observed in schizophrenia, thus underscoring the links between reelin and psychosis. The question why reelin haploinsufficiency leads to cell loss in the male but not in the female cerebellum, and how high levels of estradiol at P5 inhibit cell loss, cannot be answered yet, but recent data indicate that PCs show a peak of apoptosis during the first postnatal week in the mouse (Jankowski et al, 2009). It is tempting to speculate that PC loss in rl/+ mice is due to apoptosis, and that estradiol inhibits cell death by increasing reelin expression.…”

Natural apoptosis in developing mice dopamine midbrain neurons and vermal Purkinje cells

“…On the other hand, to be considered as an apoptotic PC, the structure observed had to fulfill the following criteria: (a) one or more fragments of highly condensed chromatin (within or reminiscent of a pyknotic nucleus) and distinct from the PC nucleolus, and (b) position within the PC layer [16].…”

“…Two time windows have been reported: in the first of these, apoptotic figures have been found at E15 [2]. In the second, dying PCs are seen from birth until P10 [16,19,25]. Thus, whereas the timing and extent of dying PCs have been addressed [16], to our knowledge, no attempts have been made to determine whether physiological PC death is related to its time of origin.…”

“…In the second, dying PCs are seen from birth until P10 [16,19,25]. Thus, whereas the timing and extent of dying PCs have been addressed [16], to our knowledge, no attempts have been made to determine whether physiological PC death is related to its time of origin. We know from previous autoradiographic studies that, in mice, cerebellar PCs are generated according to precise neurogenetic timetables [27,29].…”