Neurons expressing latexin, a carboxypeptidase A inhibitor, are restricted to lateral areas

The mammalian cerebral cortex is subdivided into a variety of functional areas having characteristic patterns of neural connectivity and neurochemical organization. A great deal of attention has been directed toward understanding when and how characteristics of regional specificity are achieved during corticogenesis (Rakic, 1988; O’Leary, 1989; Kennedy and Dehay, 1993; Levitt et al., 1993, 1997; Arimatsu, 1994; O’Leary et al., 1994). It has been largely unknown, however, whether individual cortical progenitors proliferating in the ventricular zone are restricted to a local fate, and whether specification of progenitors and postmitotic young neurons is regulated by their regional environment. Previously, we generated a monoclonal antibody, designated PC3.1, that recognizes a subset of neurons confined to the infragranular layers of lateral cortical areas in adult and early postnatal rats (Arimatsu et al., 1992). The PC3.1 antibody binds a 26 kDa protein, named latexin, which is encoded by the lxn gene that is transcribed in neurons of lateral cortex (Hatanaka et al., 1994; Jin et al., 1997). An independent biochemical study has recently revealed that latexin is able to inhibit the proteolytic activity of carboxypeptidase A in vitro (Normant et al., 1995). Many cortical latexin-immunopositive (+) neurons have the morphology of modified pyramidal cells and are glutamate+ (but not GABA+), suggesting that they are excitatory projection neurons (Arimatsu et al., 1999). The regionand lamina-specific distribution of the latexinexpressing subpopulation of glutamate+ neurons is a distinctive cellular feature that may contribute to the functional specialization of the lateral cortical areas. We demonstrated that cortical specification occurs early by showing preferential generation of latexin+ neurons in cultures derived from a lateral, rather than a dorsal, portion of the eveloping cerebral wall (Arimatsu et al., 1992). Furthermore, the in vitro capacity to generate latexin+ neurons across the cerebral wall at embryonic day 13 (E13) and E16 matched well with the distribution profile of latexin+ neurons along both dorsal-ventral and rostral-caudal axes in the adult cortex (Arimatsu and Ishida, 1998). Since developing thalamic afferents grow into the cerebral cortex at E16 or later (Catalano et al., 1991) and the corticofugal axons do not exit the cerebral cortex before E13 (Blakemore and Molnar, 1990; De Carlos and O’Leary, 1992), we have concluded that the cerebral wall is prepatterned early by elements intrinsic to the cortex rather than by connectional interactions between cortical and extracortical structures. Consistent with these results, several studies have revealed characteristics of early cortical specification (Barbe and Levitt, 1991, 1992, 1995; Dehay et al., 1993; Ferri and Levitt, 1993; Cohen-Tannoudji et al., 1994; Ebrahimi-Gaillard et al., 1994; Eagleson et al., 1997; Polleux et al., 1997; Tole et al., 1997). Thus, one of the most important questions remains: at what stage of corticogenesis are young neurons or their precursors determined to express a regional molecular phenotype? While it is possible that the fate of some 629 Development 126, 629-638 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV1363