Neuroblast

Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44 474-481 Sargeant TJ, Day DJ, Mrkusich EM, Eoo DE, Miller JH (2007) Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain. Brain Res 1175 28-38... 

In opossums, the migration from the proliferative layer shows a two-day lag between entry of neuroblasts to the lower zone (Go), with... 

Coon H., Curcio F., Sakaguchi K., Brandi M.L. and Swerdlow R.D. (1989). Cell cultures of neuroblasts from rat olfactory epithelium that show odourant responses. Proc Natl Acad Sci 86, 1703-1707. 

Doe, C. Q. (1992). Molecular markers for identified neuroblasts and ganglion mother cells in the Drosophila central nervous system. Development 116 855-863. 

This mode of regulation seems appropriate to the ERTs since their cells are already terminally differentiated, and their primary function is to grow and provide a nutrient rich incubator for the undifferentiated neuroblasts and imaginal cells that eventually produce the reproductive adult. The response of these undifferentiated progenitor cells to food withdrawal is quite unlike that of the ERTs. Larval neuroblasts and imaginal disc cells continue to proliferate for many days after a larva is starved, and seem to complete their normal proliferation programs. In this instance the ERTs lose mass, presumably as they transfer stored nutrients to the developing nervous system and the discs. 

FIG. 1. Localization of key proteins involved in the neuroblast asymmetric cell division. During late interphase a complex of proteins including Insc, Baz (and Pins) are localized to the apical cell cortex. This complex acts to mediate the basal cortical localization of the cell fate determinants Numb (and its partner Pon), Pros (and its partner Miranda) and pros RNA (and its partner Staufen) during mitosis. During interphase, Numb is cytoplasmic and Pros is localized to the apical cortex. 

A. pical cortical localisation of Pins, Insc and Bas in mitotic neuroblasts is codependent... 

FIG. 2. The formation of the apical protein complex involves two distinct steps. Bazooka is localized apically in the epithelium from which neuroblasts are derived. In the interphase (G2), delaminating neuroblast formation of the apical complex is initiated. It is thought that Baz acts to allow neuroblasts to retain the apical/basal polarity inherent in the epithelium. Baz recruits Insc to the neuroblast apical stalk during delamination before Pins becomes part of the complex. During this initiation step Baz, Insc and Pins are part of a linear hierarchy. However following delamination and during mitosis, the maintenance of the apical localization of each of these proteins requires all three proteins. 

However, in interphase delaminating neuroblasts, which are known to have completed S-phase and are at the G2 stage of the cell cycle, this codependence of Baz/Insc/Pins seen in mitotic neuroblasts does not apply. Delaminating neuroblasts possess an apical membrane stalk which retains contact with the epithelial surface and this is where apical cortical localization of Insc is initially seen (see Fig. 2). This initial localization of Insc to the apical stalk occurs... 

In Pins - embryos the initiation steps of apical complex formation occur normally. However, this complex cannot be maintained in mitotic neuroblasts. Hence, the importance of the maintenance of this complex for asymmetric cell division can be ascertained by assessing how Pins- neural progenitors divide. Pins- embryos exhibit all of the defects seen in insc mutants. Mitotic spindle orientation is defective. In the cells of mitotic domain 9 the 90° reorientation, which normally occurs in wild-type resulting in the orientation of the spindle along the apical—basal axis (Fig. 3A), fails to occur in the mutant (Fig. 3B). Mitotic spindle orientation of neuroblasts in the segmented CNS, deduced from DNA staining, also often fails to... 

Bossing T, Udolph G, Doe CQ, Technau G 1996 The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Dev Biol 179 41-64... 

Broadus J, Fuerstenberg S, Doe CQ 1998 Staufen-dependent localisation of prospero mRNA contributes to neuroblast daughter-cell fate. Nature 319 792-795... 

Skeath JB, Doe CQ 1998 Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fate in the Drosophila CNS. Development 125 1857-1865 Spana E, Doe CQ 1995 The prospero transcription factor is asymmetrically localised to the cell cortex during neuroblast mitosis in Drosophila. Development 121 3187-3195 Spana E, Doe CQ 1996 Numb antagonises Notch signaling to specify sibling neuron cell fate. Neuron 17 21—26... 

Wodarz A, Ramrath A, Kuchinke U, Knust E 1999 Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts. Nature 402 544—547 Yu F, Morin X, Cai Y, Y ang X, Chia W 2000 Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in Inscuteable apical localisation. Cell 100 399-409... 

Schaar In epithelial cells where Pins is lateral, the aster is always oriented towards the lateral surfaces. That is what is being buried when neuroblasts are being made. 

Dehner Neuroblast divisions are asymmetric not just because the cell determinants are distributed asymmetrically, but also the size of the GMC is very different, as is the nuclear size. Is nuclear size difference present from the outset If you look at cells in telophase, are the nuclei the same size ... 

Chia For the neuroblasts it is obviously different right from the start. It is clear that the GMC is much smaller. The division that we looked at carefully is the GMC division to produce two neurons. This division produces sibling neurons that have... 

Interestingly, homologues of some of the PAR proteins have been found in other metazoans where they also have a polarized distribution. For instance, in Drosophila, bagooka encodes a PAR-3 homologue that localizes to the apical surface of epithelia cells and neuroblasts moreover, bagooka is required for... 

Edgar We have looked at proliferating neuroblasts in the brain. When we coculture the brain with fat body those cells proliferate, but when we express activated ras in them without fat body, they don t proliferate. 

Edgar What about lateral inhibition in neuroblast determination This generates asymmetry that is presumably not dependent on any cell division. This is not intrinsic it relies on cell communication. There must be countless examples of this kind of asymmetry being set up. 

Nasmyth There are many examples where this is a stochastic event. Stochastic can refer to genes flicking on and off, or it can be choosing a position on the cell and marking that point — budding in yeast is a good example of this. Also, in the lateral inhibition, it is which one of the neuroblasts will win out. Once you have established this, you have created a focus for generating asymmetry. 

Eehner In string mutants, not everything works. We have heard from Bill Chia that the first neuroblast divisions follow a very stereotyped program that is also realized after transplantation or in vitro. If you do not allow divisions, the program is not realized and late neuron types are never specified. 

Neuregulins are highly expressed in the nervous system by neuroblasts, cortical neurons, peripheral sensory ganglionic cells and spinal motor neurons as well as myelinforming glia. 

Hepatocyte growth factor (HGF), also known as scatter factor, has been shown to support the survival of sympathetic neuroblasts and subpopulations of spinal motor neurons. In the former case this is apparently an autocrine effect since these cells have been shown to synthesize HGF. 

Fig. 6.1 Different strains of mice detect different concentrations of urinary odours of conspecifics with BALB/c>129/Sl>C57BL/6. Presented are the mean durations ( SEM) that mice investigated water and three sequential 2-min presentations of the same concentration of urine from one of the other strains at (A) 10 2, (B) 10 3 and (C) 10-4 concentrations. Immediatelyafter the presentation of Urine A, mice were exposed to a novel urine B (the other foreign strain) at the same concentration.(Reprinted from Neuroscience, 118, Lee, Emsley, Brown, and Hagg, T. Marked differences in olfactory sensitivity and apparent speed of forebrain neuroblast migration in three inbred strains of mice. 263-270, Copyright (2006), with permission from Elsevier)...

Lee, A.W., Emsley, J.G., Brown, R.E. and Hagg, T. (2003) Marked differences in olfactory sensitivity and apparent speed of forebrain neuroblast migration in three inbred strains of mice. Neurosci. 118,263-270. 

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