Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons.

Distinct classes of neurons are generated from progenitor cells distributed in characteristic dorsoventral patterns in the developing spinal neural tube. We define restricted neural progenitor populations by the discrete, nonoverlapping expression of Ngn1, Math1, and Mash1. Crossinhibition between these bHLH factors is demonstrated and provides a mechanism for the generation of discrete bHLH expression domains. This precise control of bHLH factor expression is essential for proper neural development since as demonstrated in both loss- and gain-of-function experiments, expression of Math1 or Ngn1 in dorsal progenitor cells determines whether LH2A/B- or dorsal Lim1/2-expressing interneurons will develop. Together, the data suggest that although Math1 and Ngn1 appear to be redundant with respect to neurogenesis, they have distinct functions in specifying neuronal subtype in the dorsal neural tube.

Postnatal development of cytochrome oxidase activity in fiber tracts of the rat brain.

This paper describes postnatal changes in cytochrome oxidase (C.O.) activity in developing fiber tracts. Quantitative histochemistry was used to measure changes in C.O. activity in nine white matter regions at postnatal days (P) 7, 12, 17, 30, and 60 in the rat. At P7, enzyme activity was maximal in the spinal trigeminal tract, medial longitudinal fasciculus, and cerebellar white matter. At P12, maximal levels were measured in the medial lemniscus and cerebral peduncle. C.O. activity increased from low levels at P7 to maximal levels by P17 in the hippocampal commissure, posterior and anterior corpus callosum, and anterior commissure. In all nine regions, C.O. activity decreased by P60. Thus, peaks in C.O. activity shifted as a function of postnatal age in a caudo-rostral direction. The regional heterogeneity in the age of onset in C.O. fluctuations suggests that vulnerability to injury and metabolic dysfunction during the perinatal period will differentially affect white matter structures, depending on the age of onset of such disruptions.

The N-terminal ERK-binding site of MEK1 is required for efficient feedback phosphorylation by ERK2 in vitro and ERK activation in vivo.

An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of MEK1 on Thr(292) and Thr(386) by ERK2, the phosphorylation and activation of ERK2 by MEK1, and the interaction of MEK1 with ERK2 and Raf-1. Deletion of the binding site from MEK1 reduced its phosphorylation by ERK2, but had no effect on its phosphorylation by p21-activated protein kinase-1 (PAK1). A MEK1 N-terminal peptide containing the binding site inhibited MEK1 phosphorylation by ERK2. However, it did not affect MEK1 phosphorylation by p21-activated protein kinase or myelin basic protein phosphorylation by ERK2. Deletion of the N-terminal ERK-binding domain of MEK1 also reduced its ability to phosphorylate ERK2 in vitro, to co-immunoprecipitate with ERK2, and to stimulate ERK2 activation in transfected cells, but it did not alter the association with endogenous Raf-1. Using ERK2-p38 chimeras and an ERK2 deletion mutant, a MEK1-binding site of ERK2 was localized to its N terminus.