vamg6792@uxa.cso.uiuc.edu (Vincent A Mazzarella) (05/19/91)
The following is a one page synopsis of a recent one-hour seminar. The impressions are my own and do not reflect accuracy of the facts contained in the presentation. Corrections and discussion are welcomed. Using a marker for opiate receptors, different compartments of the rat forebrain are distinguished: superficial (layers 2,3) cortex vs. deep (layers 5,6) cortex and "patch" areas of striatum vs. "matrix" areas of striatum. The deep cortex and patch striatum label heavily for opiate receptors, the other areas do not. Other markers, such as for cholinesterase, for example, may show a complementary pattern, but compartmentalization is maintained nevertheless. Such compartmentalization of opiate receptors appears to exist only in mammalian species, not invertebrates. Furthermore, the number of striatal patch areas in different mammalian species is constant, but the size of the patches increase with increased cell number. Neurons divide in the peri-ventricular area and then migrate outward toward the cortex. The "birthdate" of a neuron is the time when it becomes post-mitotic. If a 3H-thymidine label is injected just before a cell's birthdate, that cell will retain much label in its DNA, whereas dividing cells will dilute label taken up as they divide. Using this method of determining birthdate, the cells of the striatal patches and those of the deep cortex are seen to have early birthdates of about E13. Matrix striatal neurons and superficial cortical neurons have later birthdates, migrating around E19-20. Retrograde fluorescent label injected into substantia nigra shows projections from the striatum at E19 are primarily from patch neurons; only post- natally do matrix striatal neurons send their axons to the sub. nigra. It is suggested that as the late birthdate matrix neurons migrate to the striatum, they push apart the patch neurons, kind of like swiss cheese. Cultured, separated patch cells will re- aggregate in vitro, indicating a natural adhesiveness, but matrix cells do not. However, if an explant of the striatum is placed in the retina and allowed to develop, the patch/matrix division does not occur, suggesting some time of input may be necessary to ensure compartmentalization; patch cell adhesiveness is not sufficient. (It should be noted that striatal patch neurons will aggregate with deep cortex neurons, and that both sets of neurons have the same birthdate. Thus birthdate may be directly related to adhesiveness.) To try to determine what sort of input might be important in compartmentalization, the effect of a unilateral sub. nigra lesion at day E19 on patches was examined on the ipsilateral side and comparted to contralateral control. (It had been shown that striatal patch cells are labelled for tyrosine hydoxylase, indicating DAergic input from nigral cells.) The experiment was inconclusive, showing only a reduction in opiate receptor on the affected side, but not on number or viability of patch cells involved. Because sub nigra <--> striatum connections start to form at about E14, these lesions may be too late to be definitive. Is compartmentalization accounted for by simple clonality of a progenitor cell? Retroviruses with beta-galactosidase marker were injected into forebrain lateral ventricle in concentration sufficient to only infect 1-3 cells. Progeny of cells that incorporate the retrovirus into their genome show the beta-gal marker. It was found that clones were restricted to respective compartments. However, when chimeric animals were made from blastocysts of different mice species, the cells of each parent from a different species appeared in each compartment, therefore clonality alone does not cause compartmentalization. From a one hour seminar at Univ. of Illinois, Spring 1991: Pattern formation in developing mammalian forebrain -- Derek van der Kooy, U of Toronto -- Vincent Mazzarella College of Medicine, Neuroscience Program University of Illinois, Urbana-Champaign e-mail: mazz@vmd.cso.uiuc.edu